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caseReportBench_ClinicalDenseExtraction_Benchmark

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[ "blood pressure 115/65 mmHg, heart rate 100 beats / min, oxygen saturation rate 97 %", "blood pressure at 120 - 140/60 - 80 mmHg, heart rate 80 - 100 beats / min, oxygen saturation 100 %, body temperature 37.0 - 37.4 ℃" ]

[ "acute appendicitis", "nausea, and vomiting" ]

[ "laparoscopic appendectomy", "no abnormalities in her pediatric medical history", "Type I DM" ]

[ "headaches in her left temporal lobe", "generalized convulsions and aphasia", "In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found.", "patient was able to read but had auditory aphasia such that she could not understand spoken words", "no signs of hypotonia or amyotrophy of the limbs" ]

[ "In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found. Also, in a blood test, an increase in lactic acid was discovered ( 7.54 mM / L ).", "adenosine - to - guanine transition at t - RNA nucleotide 3243 in PCR sequencing", "The laboratory results showed hyponatremia ( 126 mEq / L ), hyperglycemia ( 257 mg / dl ), and light metabolic acidosis ( pH 7.346, PaCO 2 36.3 mmHg, HCO 3 20.1 mM / L, BE -5.3 mM / L )", "There were no abnormal findings in the chest X - ray", "Thirty minutes after inducing anesthesia, the arterial blood gas study showed pH 7.44, PaCO 2 32 mmHg, PaO 2 299 mmHg, HCO 3 23.3 mM / L, BE -2.1 mM / L; her electrolytes were Na + 125 mEq / L, K + 3.8 mEq / L, Cl - 88 mEq / L; and her blood sugar was 176 mg / dl", "The arterial blood gas study showed pH 7.32, PaCO 2 43 mmHg, PaO 2 219 mmHg, HCO 3 21.2 mM / L, and BE -3.6 mM / L; her electrolyte levels were Na + 128 mEq / L, K + 4.1 mEq / L, and Cl - 90 mEq / L; and her blood sugar level was 120 mg / dl. We then moved the patient to the ward where we performed a lactic acid test, which measured 3.6 mM / L." ]

[ "In a brain MRI and MRA, an infarction in the posterior divisions of the left mesencephalic arteries was found.", "There were no abnormal findings in the chest X - ray and electrocardiogram. One year prior to her admission to the hospital, she had an ECG that revealed a cardiac index of 67 % and no abnormal findings", "ECG results appeared normal." ]

[ "Type I DM.", "hyperglycemia ( 257 mg / dl ),", "her blood sugar was 176 mg / dl.", "her blood sugar level was 120 mg / dl." ]

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[ "23 year - old" ]

[ "age 18" ]

[ "MELAS syndrome" ]

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[ "slightly increased levels of serum aspartate aminotransferase,", "vomiting, and diarrhea", "increased serum aspartate and alanine aminotransferase levels," ]

[ "previously healthy girl", "Two months earlier, the patient 's elder sister had died of acute encephalopathy", "previously healthy" ]

[ "generalized tonic - clonic seizure and mental change, as well as increased rigidity of the extremities", "generalized tonic - clonic seizure.", "drowsy and showed decerebrate rigidity, without focal neurologic signs", "His mental state improved, and on the fourth day of hospitalization he was almost alert. Cognitive functions gradually improved, though severe motor deficits remained." ]

[ "symmetric low - density lesions in the thalami and external capsules", "symmetric T1- and T2 - prolonged areas were present in the thalami and external capsules. T2 * -weighted gradient - echo images clearly showed that within the thalamic lesions, acute hemorrhage had occurred. After the intravenous administration of gadolinium - diethylene triamine penta - acetic acid, the lesions showed no abnormal enhancement and ADC mapping revealed areas of low signal intensity within them ( Fig. 2A ). Localized proton MR spectroscopy using a stimulated echo - acquisition mode sequence ( TR / TE=3000/30, 96 acquisitions, volume of interest=7 mL ) showed a small doublet at 1.33 ppm ( Fig. 2B ). Laboratory findings indicated slightly increased levels of serum aspartate aminotransferase, lactate, and ammonia, though the lactate level rapidly returned to normal. CSF analysis revealed increased protein content without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for DNA of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA.", "symmetric low - density thalamic lesions", "symmetric distribution of T1- and T2 - prolonged areas in the thalami ( Fig. 1A ), tegmentum of the pons, and periventricular white matter. T2 * -weighted gradient - echo images ( TR / TE = 800/30, flip angle = 20 ° ) demonstrated low signal intensities within the thalamic lesions, suggesting acute hemorrhage ( Fig. 1B ). After the intravenous administration of gadolinium - diethylene triamine penta - acetic acid, the lesions showed no abnormal enhancement. Diffusion - weighted MR imaging ( b value=1000 sec / mm 2 ) demonstrated high signal intensity in all the lesions, though this was absent in the central portion of thalamic lesions, and other than in this same area, apparent diffusion coefficient ( ADC ) mapping revealed low signal intensity ( Fig. 1C ). Localized proton MR spectroscopy of the thalami using a stimulated echo - acquisition mode sequence ( TR / TE=3000/30, 96 acquisitions, volume of interest=7 mL ) showed that compared with an age - matched control subject, peak intensities were higher, occurring at 2.0 - 2.5 and 0.8 - 1.5 ppm ( Figs. 1D, E ). Laboratory findings on admission showed increased serum aspartate and alanine aminotransferase levels, though those of blood ammonium and lactate were normal. Cerebrospinal fluid ( CSF ) analysis showed slightly increased protein content, without pleocytosis. Polymerase chain reaction analysis of the CSF was negative for deoxynucleic acid ( DNA ) of herpes simplex virus and enterovirus, and similar analysis of peripheral blood was negative for major mutations in mitochondrial DNA", "residual atrophic change in the previously observed lesions; both T1- and T2 - weighted images depicted small areas of high signal intensity at the center of the thalami, indicating residual subacute hemorrhage. ' }" ]

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[ "cough, and rhinorrhea," ]

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[ "6 - month - old", "10 - month - old" ]

[ "6 - month - old", "10 - month - old" ]

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[ "she died at the age of 84", "CK levels in all her four sons were found to be elevated and her third son was diagnosed with epilepsy", "She and her fourth son had also been previously diagnosed with Hashimoto thyroiditis ( Fig. 1 )", "hypothyroidism", "family history of bent spine, i.e., in her elder sister ( patient 2, Fig. 1, III-5 ), mother ( Fig. 1, II-3 ), and maternal aunt ( Fig. 1, II-4 )" ]

[ "presenting with tremors since the age of 60", "she started walking with the aid of a walking stick", "At 82 years of age, she was hospitalized for generalized seizures and disturbed consciousness", "Brain MRI revealed hyperintense lesions around the white matter ( Fig. 2 f );", "gait disturbance.", "she started using a walking stick because of her unstable gait", "gradually became more difficult for her to climb the stairs.", "right ptosis, dysarthria,", "eye movements were normal.", "Tendon reflexes were symmetrical, and Babinski ’s sign was absent. She had poor balance with tandem gait without limb ataxia. Sensory systems were intact and Romberg ’s sign was negative. She scored poorly on the attention and calculation tests that are a part of the Mini - Mental State Examination ( score : 25 points )", "Brain MRI studies revealed several differences between the patients 1 and 2. d Axial FLAIR images of patient 1 show moderate cerebellar atrophy and some cerebral cortical atrophy. f The same images of patient 2 revealing hyperintense lesions around the white matter", "Brain magnetic resonance imaging ( MRI ) with fluid - attenuated inversion recovery imaging showed moderate cerebellar and temporo - parieto - occipital lobe atrophy ( Fig. 2 d ). MR spectroscopy revealed the absence of increased lactate peaks. 123I - IMP single photon emission CT revealed hypoperfusion that was indicative of atrophic brain lesions." ]

[ "CT of T10 revealed severe atrophy and fatty degeneration of the paraspinal muscles ( Fig. 2 e ). Brain MRI revealed hyperintense lesions around the white matter ( Fig. 2 f ); elevated serum and CSF lactate levels were also noted at this time. The mitochondrial DNA analysis of the lymphocytes did not indicate MELAS ( m.3243A > G ) or MERRF ( m.8344A > G ) mutations", "Sixty - nine of the 609 Gomori trichrome stained muscle fibers ( 11.3 % ) were ragged - red fibers ( Fig. 3 a ). Cytochrome c oxidase ( COX ) activity was deficient in many of the ragged - blue fibers that were stained with succinate dehydrogenase ( SDH ) and COX ( 233 of 881 muscle fibers, 26.4 % ) ( Fig. 3 b, c ), and no blood vessels showing strong SDH reactivity were observed. In NADH dehydrogenase - reactive sections, focal decreases and increases in oxidative enzyme activities were observed. Adenosine monophosphate ( AMP ) deaminase activity was normal. The random checkerboard distribution of the histochemical fiber types was preserved as shown in the ATPase - reactive sections. Acid phosphatase activity was slightly high in some fibers. Muscle fiber glycogen contents appeared normal and the lipid contents were slightly high in some fibers. Electron microscopy showed abnormal proliferation of mitochondria with paracrystalline inclusions ( Fig. 4 ). Fig. 3 Histochemical analysis of the right biceps brachii muscle. a Gomori trichrome staining reveals typical ragged - red fibers. Histochemical analysis of serial sections of samples stained with b SDH or c COX shows a number of ragged - blue fibers with COX deficiency. a−c Bar 100 μm Fig. 4 Electron micrograph of abnormal mitochondria in the right biceps brachii muscle. Abnormal mitochondria with paracrystalline inclusions", "m.602C > T in the tRNA Phe gene and m.16111C > G in the D - loop. The variant m.16111C > G is listed as a polymorphism, but the variant m.602C > T is not reported in either database. The m.602C > T variant was also confirmed by direct sequencing. The sequence chromatogram showed a heteroplasmic m.602C > T transition in the muscle homogenate mitochondrial tRNA Phe gene ( Fig. 5 a ). The proportion of mutant mitochondrial DNA in the muscle was 64.7 ± 1.2 % ( mean ± SD; the operation was performed thrice ). Mutant mitochondrial DNA was not detected in the blood lymphocytes", "elevated serum CK levels", "Axial FLAIR images of patient 1 show moderate cerebellar atrophy and some cerebral cortical atrophy. f The same images of patient 2 revealing hyperintense lesions around the white matter Laboratory data were as follows : serum CK level was 290 IU / l ( normal range 45–163 IU / l ), resting blood and cerebrospinal fluid ( CSF ) lactate levels were normal, thyroid - stimulating hormone levels were slightly low at 0.47 μIU / ml ( normal range 0.5–5.0 μIU / ml ). Under the administration of 50 μg / day levothyroxine; antithyroglobulin antibody levels were high at 7.0 U / ml ( normal range < 0.3 U / ml ), antithyroid peroxidase antibody levels were high at 46.5 U / ml ( normal range < 0.3 U / ml ), rheumatoid factor levels were high at 152.3 IU / ml ( normal value < 15.0 IU / ml ), antinuclear antibody levels were mildly elevated ( titer of 1:80 ). Autoimmune analyses, including anti - Jo-1, anti - RNP, anti - SS - A, and anti - SS - B, were negative. The oral glucose tolerance test ( 75 g ) was within normal limits", "Computed tomography ( CT ) of the thoracic spinal nerve 10 ( T10 ) revealed severe atrophy and fatty degeneration of the paraspinal muscles ( Fig. 2 c ). Brain magnetic resonance imaging ( MRI ) with fluid - attenuated inversion recovery imaging showed moderate cerebellar and temporo - parieto - occipital lobe atrophy ( Fig. 2 d ). MR spectroscopy revealed the absence of increased lactate peaks. 123I - IMP single photon emission CT revealed hypoperfusion that was indicative of atrophic brain lesions. ',", "All respiratory chain enzyme activities, which are expressed as a percentage of the normal control values relative to the citrate synthase activity, were greater than 20 % ( Table 1 ). BN - PAGE revealed no abnormalities in either the respiratory chain complexes or their molecular assembly structures. Table 1 Enzymatic activities for mitochondrial respiratory complexes in patient 1 CI activity ( CI / CS ) CII activity ( CII / CS ) CIII activity ( CIII / CS ) CIV activity ( CIV / CS ) CS activity Patient 1 0.1938 ( 0.7027 ) 0.2723 ( 0.9874 ) 1.2737 ( 4.6192 ) 0.0579 ( 0.21 ) 0.2757 Control 0.3194 ( 1.6183 ) 0.2751 ( 1.3444 ) 1.3132 ( 6.5512 ) 0.0826 ( 0.3840 ) 0.2151 Patient 1 / control ratio 60.7 % ( 43.4 % ) 98.9 % ( 73.4 % ) 97.0 % ( 70.5 % ) 70.1 % ( 54.7 % ) Enzymatic activities for individual mitochondrial respiratory complexes are given in nmol / min protein, and represent percentage of normal control ( n = 10 ) mean relative to a reference enzyme of citrate synthase ( CS ) The activities are relatively low in complex I and complex IV compared with other complexes" ]

[ "Holter monitoring revealed high - frequency premature contractions." ]

[ "She and her fourth son had also been previously diagnosed with Hashimoto thyroiditis ( Fig. 1 ).", "hypothyroidism", "thyroid - stimulating hormone levels were slightly low at 0.47 μIU / ml ( normal range 0.5–5.0 μIU / ml ).", "Under the administration of 50 μg / day levothyroxine; antithyroglobulin antibody levels were high at 7.0 U / ml ( normal range < 0.3 U / ml ), antithyroid peroxidase antibody levels were high at 46.5 U / ml ( normal range < 0.3 U / ml ),", "The oral glucose tolerance test ( 75 g ) was within normal limits," ]

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[ "with a stooping posture", "she started walking with the aid of a walking stick", "abnormal posture and gait disturbance", "slight stooping posture and a pushed - out waist", "she started using a walking stick because of her unstable gait.", "gradually became more difficult for her to climb the stairs", "prominent paraspinal muscle atrophy and mild proximal weakness of limbs", "marked atrophy of the paraspinal muscles and abnormal posture", "right ptosis, dysarthria", "moderate weakness of the neck flexion and mild weakness of the proximal limb muscles", "pushed - out waist", "marked atrophy of the paraspinal muscles", "Needle electromyographic findings of the biceps brachii and rectus femoris muscles indicated mild myopathic features." ]

[ "bilateral cataracts, and hearing loss", "eye movements were normal", "Pure - tone audiometry indicated sensorineural and high - frequency hearing loss." ]

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[ "84 - year - old", "73 - year - old" ]

[ "age of 60", "age of 63" ]

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[ "swallowing problems and gastroesophageal reflux" ]

[ "second child of nonconsanguineous parents who was born after an uneventful pregnancy of 42 weeks", "positive family history of minicore myopathy ( his sister died with this condition at age 5 due to aspiration )", "The parents were heterozygous carriers ( Wortmann et al. 2009 )" ]

[ "congenital hypotonia, low facial expression, and inverted feet.", "facies myopathica", "the boy could not sit up, raise his arms above the level of the hips, hold a pen, or stand due to his severe, generalized muscle weakness and contractures. Further physical signs were bilateral ptosis, facies myopathica with open mouth, and kyphoscoliosis in addition to joint contractures, presenting foremost in his hips and knees" ]

[ "chronic lactic acidemia ( lactate 2.3–4 mmol / l, C : < 2.1 mmol / l ), 3 - methylglutaconic aciduria ( 80 μmol / l, C : < 18 μmol / mmol creatinine ), and recurrent hypoglycemic episodes. Serum alanine levels ( 610 μmol / l, C : < 450 μmol / l ) and creatine kinase ( CK ) levels ( 500–800 U / l, C : 180 U / l ) were moderately increased", "The biopsy results showed the characteristic picture of central core disease : electron microscopy detected abnormal, large mitochondria with crystalline inclusions and biochemical evidence of severe mitochondrial dysfunction ( Table 1 ). Genetic studies including mitochondrial DNA sequencing, sequencing of the nuclear - coded structural complexes I and III genes, and POLG mutation analysis were all normal. A compound heterozygous RYR1 mutation in complementary DNA ( cDNA ) was found.", "Biochemistry ATP production nmol / h / mUCS ( N 42–81 ) 4 Complex I mU / UCS ( N 70–251 ) 58 Complex II mU / UCS ( N 335–749 ) 312 Complex III mU / UCS ( N 2200–6610 ) 725 Complex IV mU / UCS ( N 810–3120 ) 483 Complex deficiencies I, II, III, IV", "Genetics Paternal mutation p. His581GlnfsX29 ( exon 16 ) Maternal mutation p. Val14849Ile ( exon 101 )" ]

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[ "recurrent hypoglycemic episodes." ]

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[ "congenital hypotonia, low facial expression, and inverted feet.", "swallowing problems", "hyperlaxity with arachnodactyly", "initial histological findings suggested a possible multi / minicore disease", "creatine kinase ( CK ) levels ( 500–800 U / l, C : 180 U / l ) were moderately increased", "No motor development was observed with regular physiotherapy", "The biopsy results showed the characteristic picture of central core disease : electron microscopy detected abnormal, large mitochondria with crystalline inclusions and biochemical evidence of severe mitochondrial dysfunction ( Table 1 ).", "At age 9 years, while receiving regular physiotherapy, the boy could not sit up, raise his arms above the level of the hips, hold a pen, or stand due to his severe, generalized muscle weakness and contractures", "bilateral ptosis, facies myopathica with open mouth, and kyphoscoliosis in addition to joint contractures, presenting foremost in his hips and knees", "He had no extraocular muscle anomalies and no exercise - induced myalgia" ]

[ "low - set ears, hypermetropia" ]

[ "Dysmorphic features included brachyturricephaly, facies myopathica" ]

[ "born after an uneventful pregnancy of 42 weeks" ]

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[ "At birth" ]

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[ "RYR1" ]

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[ "The patient 's mother ( II-2 ) and uncle ( II-3 ) also had optic neuropathy, but other neurological abnormalities such as ataxia and dystonia were not observed. The patient 's mother has a history of subarachnoid hemorrhage. MRI of his mother disclosed mild atrophy of the optic nerve ( Fig. 2E ), pons, and cerebellum ( Fig. 2F - H ). No signal changes were observed in the inferior olivary nucleus ( Fig. 2F - H ). We were unable to confirm the detailed clinical information of the proband 's grandmother ( I-2 ). \"" ]

[ "gait disturbances", "horizontal gaze palsy, gaze - evoked nystagmus, dysarthria, and cerebellar ataxia", "Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus", "severe dizziness and double vision", "gait disturbances", "mild disturbance of cognitive function ( Revised Wechsler Adult Intelligence Scale : total IQ=73, performance IQ=58, verbal IQ=91 )", "Neurological disturbances were observed including bilateral exotropia, double vision, incomplete horizontal movement of the eyes to the bilateral side, horizontal, and vertical gaze - evoked nystagmus, and dysarthria. The light reflex was prompt. No disturbances in cranial nerves I, VII, VIII, and XII were detected. Tremor appeared in his neck, but other involuntary movements including palatal myoclonus were not observed. While his upper and lower limbs showed no paralysis, they exhibited severe cerebellar ataxia and hypotonia. No abnormal findings were detected in his deep tendon reflex and sensory system.", "Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ),", "brain MRI disclosed severe atrophy of the cerebellum and mild atrophy of the brain stem ( Fig. 2B ). The bilateral inferior olivary nucleus exhibited low signal intensities on T1 - weighted imaging, and high signal intensities on T2 - weighted imaging, suggesting degeneration ( Fig. 2C and D )." ]

[ "Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus", "Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations.", "Blood and cerebrospinal fluid analyses were normal", "Ergometer exercise did not up - regulate his serum lactate and pyruvate", "Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A ), and brain MRI disclosed severe atrophy of the cerebellum and mild atrophy of the brain stem ( Fig. 2B ). The bilateral inferior olivary nucleus exhibited low signal intensities on T1 - weighted imaging, and high signal intensities on T2 - weighted imaging, suggesting degeneration ( Fig. 2C and D ).", "The G11778A and T3394C mutations were identified, while the A3243 G mutation was not detected.", "Sequence analysis revealed the homoplasmic T3394C mutation of the mtDNA ( Fig. 3A ). This mutation causes a Tyr - to - His amino acid substitution in ND1. PCR - RFLP data revealed that the T3394C mutation present in both the proband ( III-1 ) and his mother ( II-2 ) was homoplasmic; differences between the patient and his mother were not observed for this mutation ( Fig. 3B ). The G11778A mutation, which causes an Arg - to - His amino acid substitution in ND4, was also observed ( Fig. 4A ). PCR - RFLP data showed that this mutation in the patient and his mother was heteroplasmic ( Fig. 4B ). The semiquantitative analysis performed to determine the effect of this mutation on disease severity revealed that III-1 had a 92 % heteroplasmic G11778A mutation, and II-2 had a 70 % heteroplasmic G11778A mutation ( Fig. 4C )." ]

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[ "visual and gait disturbances", "horizontal gaze palsy, gaze - evoked nystagmus", "atrophy of the optic nerve", "severe dizziness and double vision", "visual and gait disturbances", "bilateral exotropia, double vision, incomplete horizontal movement of the eyes to the bilateral side, horizontal, and vertical gaze - evoked nystagmus", "The light reflex was prompt.", "atrophy of the optic nerve", "no pigmentation changes of the retina", "Orbital MRI revealed atrophy of the optic nerve ( Fig. 2A )," ]

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[ "37 - year - old" ]

[ "10 years of age" ]

[ "LHON plus olivocerebellar degeneration" ]

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[ "162 centimeters tall and 30 kilograms in weight.", "Her vital signs were stable" ]

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[ "no family history of neurological diseases", "Motor and intellectual development was normally attained during infancy.", "hospitalized for general muscle weakness and gait disturbance when she was 6 years old.", "24 years old she had sudden syncope", "when the patient was 26, she had another stroke" ]

[ "left hemiplegia and aphasia", "Motor and intellectual development was normally attained during infancy", "general muscle weakness and gait disturbance", "decreased muscle tone and strength, and atrophic muscle mass", "sudden syncope", "An magnetic resonance imaging ( MRI ) revealed acute infarction of the left basal ganglia and the left frontal lobe.", "another stroke and presented with general weakness, aphagia, and dysarthria", "An MRI showed old multifocal infarctions at the basal ganglia, thalamus, left pons and left periventricular white matter area. An MR spectroscopy showed a positive lactate peak in both basal ganglia.", "presented with another stroke with associated left sided weakness", "An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ).", "The patient 's mental status and general condition improved" ]

[ "The biopsy showed mitochondrial myopathy of the pleoconial type", "Her first echocardiography was completed afterwards and showed marked hypertrophy of both ventricles without any regional wall problems.", "An magnetic resonance imaging ( MRI ) revealed acute infarction of the left basal ganglia and the left frontal lobe", "An MRI showed old multifocal infarctions at the basal ganglia, thalamus, left pons and left periventricular white matter area. An MR spectroscopy showed a positive lactate peak in both basal ganglia", "The plasma lactate level was 21.8 mg / dL ( normal range 4.5 - 19.8 mg / dL ). CBC, electrolyte, blood urea nitrogen, and creatinine were in the normal range. Thyroid function was also measured. The free T4 was 1.76 ng / dL ( normal range 0.89 - 1.76 ng / dL ) and TSH was 0.04 µIU / mL. Levels of complement component 3 and 4 were 13 mg / dL ( normal range 75 - 145 mg / dL ) and 18 mg / dL ( normal range 12 - 72 mg / dL ) respectively. Antistreptolysin O antibody was negative, rheumatoid factor was negative, and anti - double stranded DNA was 1.6 ( normal range 0 - 6 ). Lupus anticoagulants and anti cytoplasmic antibody, which were measured to rule out vasculitis, were normal. A DNA gene sequencing study showed a mutation : m.3303C > T mutation in the mitochondrially encoded tRNA leucine 1 gene, which confirmed the diagnosis of MELAS syndrome.", "no specific findings in chest X - rays", "Her MRI revealed infarction in the right middle cerebral territory ( Fig. 1 ). An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ). An echocardiography was performed to identify the cardiac origin of the ischemic stroke, and it showed concentrically hypertrophied left ventricle with globally hypokinetic wall motion and ejection fraction of 25 %. An intracardiac thrombus attached to the left ventricular apex was noted ( Fig. 3 )." ]

[ "Her first echocardiography was completed afterwards and showed marked hypertrophy of both ventricles without any regional wall problems.", "no specific findings in chest X - rays or electrocardiography", "An magnetic resonance angiography showed an occluded right distal internal carotid artery and right middle cerebral artery ( Fig. 2 ).", "An echocardiography was performed to identify the cardiac origin of the ischemic stroke, and it showed concentrically hypertrophied left ventricle with globally hypokinetic wall motion and ejection fraction of 25 %. An intracardiac thrombus attached to the left ventricular apex was noted ( Fig. 3 )." ]

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[ "general muscle weakness and gait disturbance", "decreased muscle tone and strength, and atrophic muscle mass.", "consistent muscle weakness", "mitochondrial myopathy of the pleoconial type" ]

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[ "She was born after a normal pregnancy and delivery." ]

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[ "27 - year - old" ]

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[ "MELAS syndrome" ]

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[ "blood pressure of 111/59 mm Hg, pulse rate of 109 beats / min, respiratory rate of 20 / min, and body temperature of 36.0 ℃.", "blood pressure of 209/147 mm Hg, pulse rate of 140 beats / min, respiratory rate of 25 / min, and body temperature of 36.5 ℃" ]

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[ "frequent and insidious onset of seizure - like episodes, dysarthria, gait disturbance and a right - sided visual field defect that had started four years ago without any history of essential hypertension, diabetes mellitus and dyslipidemia." ]

[ "seizure - like episode lasting for approximately five minutes and subsiding spontaneously", "frequent and insidious onset of seizure - like episodes, dysarthria, gait disturbance and a right - sided visual field defect that had started four years ago", "Laboratory results were raised cerebrospinal fluid ( CSF ) lactate of 5.2 mmol / L.", "Electroencephalography ( EEG ) showed diffuse cerebral dysfunction", "Electromyography revealed sensorimotor polyneuropathy and chronic myopathy", "Brain MRI showed infarction in the right temporal lobe, ischemia in the left posterior frontoparietal cortex and basal ganglia, and cystic lesion in the pineal gland with brainstem and cerebellar atrophy ( Fig. 1 ).", "Biopsy of left vastus lateralis showed neurogenic atrophy and slightly increased lipid vacuoles without paracrystalline inclusion in the mitochondria", "Five minutes after local anesthesia with lidocaine, her consciousness changed suddenly", "stuporous", "recovered consciousness" ]

[ "Laboratory results were raised cerebrospinal fluid ( CSF ) lactate of 5.2 mmol / L.", "Brain MRI showed infarction in the right temporal lobe, ischemia in the left posterior frontoparietal cortex and basal ganglia, and cystic lesion in the pineal gland with brainstem and cerebellar atrophy ( Fig. 1 ).", "Transthoracic echocardiography revealed decreased early diastolic mitral annulus velocity ( E ' velocity ) and abnormal myocardial texture which were possibly associated with the initial phase of restrictive cardiomyopathy" ]

[ "electrocardiography ( ECG ) showed supraventricular tachycardia", "follow - up ECG showed sinus rhythm with pre - excitation", "Transthoracic echocardiography revealed decreased early diastolic mitral annulus velocity ( E ' velocity ) and abnormal myocardial texture which were possibly associated with the initial phase of restrictive cardiomyopathy", "followed up without tachycardia attack." ]

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[ "Electromyography revealed sensorimotor polyneuropathy and chronic myopathy", "Biopsy of left vastus lateralis showed neurogenic atrophy and slightly increased lipid vacuoles without paracrystalline inclusion in the mitochondria" ]

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[ "21 - year - old" ]

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[ "MELAS syndrome" ]

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[ "diagnosed with mitochondrial myopathy, encephalopathy and stroke - like episodes ( MELAS ) at age 32 after suffering a fall at her job that was thought to be secondary to a seizure.", "Her family history is significant for a 12 - year - old daughter who is currently asymptomatic and a sister who also carries the diagnosis of MELAS but is less severely affected with symptoms mainly of diabetes mellitus and hearing loss" ]

[ "a fall at her job that was thought to be secondary to a seizure", "she was no longer able to be employed and her husband became her primary caretaker", "sensorineural hearing loss", "bilateral ophthalmoplegia, ptosis, seizures and stroke - like episodes with concern for dementia", "Her brain MRI demonstrated extensive cerebral atrophy especially involving the temporal lobes ( R > L ), and moderate cerebellar atrophy with extensive white matter disease." ]

[ "positive results for the A - to - G transition at nucleotide 3243 ( m.3243A > G ) of the mitochondrial genome, with 25 % heteroplasmic deleterious mutation in MT - TL1, a mitochondrial leucine transfer RNA gene", "an echocardiogram demonstrated symmetric left ventricular hypertrophy with normal ventricular systolic function, and her cardiac MRI showed extensive positive late gadolinium enhancement in the sub - epicardium of approximately 25–50 % in thickness in the inferior segment at the base, inferior to lateral segments at the mid - ventricle and lateral segment of the apex, with sparing of the endocardium and septum", "Her brain MRI demonstrated extensive cerebral atrophy especially involving the temporal lobes ( R > L ), and moderate cerebellar atrophy with extensive white matter disease", "Monitoring laboratory evaluation yielded no significant abnormalities with the exception of a slightly elevated brain natriuretic peptide of 305 ( normal < 200 ng / L ). Her liver and kidney functions were normal and there was no hyperglycemia." ]

[ "progressive left ventricular hypertrophy ( LVH ) on echocardiogram", "cardiac work - up included an EKG which showed sinus rhythm with frequent normally conducted premature atrial contractions and a Holter monitor that demonstrated episodes of non - sustained atrial tachycardia", "an echocardiogram demonstrated symmetric left ventricular hypertrophy with normal ventricular systolic function, and her cardiac MRI showed extensive positive late gadolinium enhancement in the sub - epicardium of approximately 25–50 % in thickness in the inferior segment at the base, inferior to lateral segments at the mid - ventricle and lateral segment of the apex, with sparing of the endocardium and septum", "slightly elevated brain natriuretic peptide of 305 ( normal < 200 ng / L )." ]

[ "no hyperglycemia." ]

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[ "myopathy", "bilateral ophthalmoplegia, ptosis" ]

[ "sensorineural hearing loss,", "bilateral ophthalmoplegia, ptosis," ]

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[ "44 - year - old" ]

[ "age 32" ]

[ "mitochondrial myopathy , encephalopathy and stroke - like episodes ( MELAS )" ]

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[ "vomiting.", "anorexia" ]

[ "previously healthy", "generalized tonic - clonic seizures", "In 1989, hearing impairment was first documented and ascribed to the previous encephalitis", "recurrent admissions for seizures,", "In 1999, he was diagnosed with diabetes mellitus", "The patient 's sister was admitted to our department in October 2010 with gross oedema of the legs. Her medical history included diabetes and sensorineural deafness. Advanced renal impairment was noted. In view of her phenotype, we suspected maternally inherited diabetes and deafness ( MIDD ). The 3243A > G mutation in the MT - TL1 gene of the mitochondrial DNA ( mtDNA ) was subsequently demonstrated in blood leucocytes, confirming the diagnosis", "The patient now lives in a nursing home" ]

[ "headache", "Meningism, but no focal neurological signs, was noted on examination", "slight elevation of protein in the cerebrospinal fluid ( CSF ) but no increased cell count", "right - sided weakness developed", "Electroencephalogram demonstrated left parieto - occipital focal slowing", "Results of T1 / T2 - weighted brain magnetic resonance imaging were reported to be in keeping with an inflammatory process in the left occipital area", "generalized tonic - clonic seizures", "No residual neurological deficits persisted", "recurrent admissions for seizures", "patient 's functional status deteriorated progressively", "In the initial CSF analysis, no lactate levels had been checked.", "CT scan of the brain showed diffuse cerebral atrophy, bilateral basal ganglia calcification and a left parieto - occipital hypodensity, likely representing a previous stroke - like event", "Cerebral computed tomography of a 40 - year - old man showing generalized cerebral atrophy, bilateral basal ganglia calcification ( asterisks ) and a left parieto - occipital hypodensity ( arrow )" ]

[ "slight elevation of protein in the cerebrospinal fluid ( CSF ) but no increased cell count", "Results of T1 / T2 - weighted brain magnetic resonance imaging were reported to be in keeping with an inflammatory process in the left occipital area.", "herpes serology came back negative", "In the initial CSF analysis, no lactate levels had been checked", "CT scan of the brain showed diffuse cerebral atrophy, bilateral basal ganglia calcification and a left parieto - occipital hypodensity, likely representing a previous stroke - like event", "demonstration of the 3243A > G transition in blood and urine. The heteroplasmy rate ( the mixture of normal and mutated mitochondrial DNA ) was 50 and 90 %, respectively", "Cerebral computed tomography of a 40 - year - old man showing generalized cerebral atrophy, bilateral basal ganglia calcification ( asterisks ) and a left parieto - occipital hypodensity ( arrow" ]

[ "Electrocardiogram showed Wolff – Parkinson – White syndrome" ]

[ "diagnosed with diabetes mellitus, requiring insulin straightaway." ]

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[ "hearing impairment", "Macular dystrophy, but no signs of diabetic retinopathy, was found on fundoscopy" ]

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[ "18 - year - old" ]

[ "18 - year - old" ]

[ "Mitochondrial encephalopathy with lactic acidosis and stroke - like episodes ( MELAS )" ]

[ "treatment with coenzyme Q 10 was started" ]

[ "he had a short stature one standard below the mean with a BMI within normal limits." ]

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[ "A 17 - year - old Venezuelan male with a 5 - year past medical history of bilateral ptosis came for his regular ophthalmic and general health checkup ( Fig. 1 ). He had diplopia, decreased visual acuity and nyctalopia. He was diagnosed with diplopia by a general practitioner 5 years ago since then the patient has not seen any physician for any eye examination or general health checkup. His personal and family history was non - significant.", "5 - year past medical history of bilateral ptosis", "His personal and family history was non - significant" ]

[ "bilateral and partial external ophthalmoplegia with mild limitations in gaze in all directions;", "MRI brain, echo, audiometry, urine analysis, serum creatinine kinase, lactate and pyruvate levels, basic metabolic panel, calcium, magnesium, plasma cortisol levels and thyroid profile were normal", "His CSF protein and lactate levels were elevated", "chronic external ophthalmoplegia", "Bilateral ptosis" ]

[ "MRI brain, echo, audiometry, urine analysis, serum creatinine kinase, lactate and pyruvate levels, basic metabolic panel, calcium, magnesium, plasma cortisol levels and thyroid profile were normal", "His CSF protein and lactate levels were elevated", "A biopsy of the anterior right tibial muscle showed a higher concentration of mitochondria with notable abnormalities in size, form and disposition of mitochondrial crests" ]

[ "echo, audiometry, urine analysis, serum creatinine kinase, lactate and pyruvate levels, basic metabolic panel, calcium, magnesium, plasma cortisol levels and thyroid profile were normal", "EKG, which unveiled complete right branch block, and a left anterior hemiblock", "The Holter monitor recorded supraventricular extrasystoles and a defect in ventricular repolarization", "cardiac conduction defects", "Electrocardiogram revealing a complete right bundle branch block and a left anterior hemiblock" ]

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[ "He had diplopia, decreased visual acuity and nyctalopia", "bilateral and partial external ophthalmoplegia with mild limitations in gaze in all directions; visual acuity was four bilaterally with evidence of hypermetric astigmatism.", "On funduscopic examination, bilateral atypical pigmentary retinopathy was seen", "audiometry, urine analysis, serum creatinine kinase, lactate and pyruvate levels, basic metabolic panel, calcium, magnesium, plasma cortisol levels and thyroid profile were normal", "chronic external ophthalmoplegia", "pigmentary retinopathy", "Bilateral ptosis", "Funduscopic examination showing atypical pigmentary retinitis" ]

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[ "17 - year - old" ]

[ "onset of disease before 20 years of age" ]

[ "The diagnosis of KSS was made from the following findings" ]

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[ "835 g ( −0.5 SDS )," ]

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[ "A 30‐year‐old primigravid woman, with a so far uneventful pregnancy, was referred to our clinic with polyhydramnios", "Aside from a spontaneously closed ventricular septal defect ( VSD ) in her own infancy, both parents were healthy", "A maternal uncle of the mother had died postnatally of an unknown cause", "The mother was pregnant again before exome sequencing had started", "Amniocentesis with sequence analysis of the FBXL4 gene confirmed that the fetus was unaffected. The pregnancy resulted in the birth of a healthy child.", "The VSD in our patient is considered to be a separate finding ( familial trait )" ]

[ "mild dilatation of both lateral ventricles ( 11 mm ).", "showing an enlarged cisterna magna ( 12 mm ) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm ( slightly below p3, with head circumference p50, Fig. 1 A ).", "hypotonic infant", "Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy.", "Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst ( Figure S1C ), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst ( Figure S1D )", "brain abnormalities on more detailed fetal ultrasound examination", "hypotonia and diminished fetal movements", "mitochondrial encephalomyopathy", "cerebellar atrophy", "hypotonic", "poor condition with need for mechanical ventilation," ]

[ "First‐trimester combined test revealed a low risk for trisomies ( NT 1.1 mm ).", "The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50.", "More detailed fetal intracranial assessment was possible afterwards, showing an enlarged cisterna magna ( 12 mm ) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm ( slightly below p3, with head circumference p50, Fig. 1 A ). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD", "QF PCR and a CytoScan HD Array were performed, showing a small de novo duplication on chromosome 11 ( 11q22.1 ), including exon 1 of the contactine 5 ( CNTN5 ) gene.", "Maternal serum infection testing ( TORCHES ) was also normal", "Postnatal cardiac ultrasound confirmed the presence of a small VSD.", "Cranial ultrasound on first postnatal day showed bilateral peri‐ and intraventricular hemorrhages with dilatation of the ventricles, periventricular pseudocysts, and confirmed the presence of cerebellar atrophy.", "progressive lactate acidosis with extremely high plasma lactate : 19.1 mmol / L and high pyruvate : 269 μ mol / L. The L / P ( lactate / pyruvate ) ratio was 71, which is strongly increased ( normal < 20 ). Organic acid analysis in urine showed a strong increase of lactate ( 56540 μ mol / mmol creatinine ) and increases of 3‐OH‐butyrate, pyruvate, fumarate, malate, and 4‐OH‐phenyllactate. The amino acids proline and lysine were increased in both urine and plasma. Oligosaccharides in urine and acylcarnitines and very long‐chain fatty acids in plasma were normal", "Postmortem cranial MRI confirmed the findings on ultrasound, showing extensive bilateral intra‐ and periventricular hemorrhage with adjacent cyst ( Figure S1C ), vermian and cerebellar hypoplasia with a retrocerebellar pseudocyst ( Figure S1D )", "DNA analysis of the PDHA1 ‐gene ( most frequent genetic cause of pyruvate‐dehydrogenase complex deficiency ) showed no pathogenic mutations", "Targeted exome analyses of a panel of 447 nuclear genes were performed, containing known mitochondrial disease genes and functionally or clinically related genes. Two heterozygous mutations in the FBXL4 gene were detected and confirmed by Sanger sequencing : c.292C > T ( p.(Arg98*))and c.1303C > T ( p.(Arg435 * ) ).", "brain abnormalities on more detailed fetal ultrasound examination", "persistent lactate acidosis" ]

[ "spontaneously closed ventricular septal defect ( VSD ) in her own infancy,", "The myocardium was hypertrophic with a small perimembraneous VSD", "Postnatal cardiac ultrasound confirmed the presence of a small VSD", "hypotension", "The VSD in our patient is considered to be a separate finding ( familial trait )" ]

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[ "Testes were not palpable in the scrotum" ]

[ "respiratory distress syndrome.", "poor condition with need for mechanical ventilation" ]

[ "He had relatively long and slender arms and legs, large hands, long fingers, small fingernails and somewhat broad distal phalanges", "The lower extremities showed bilateral pes cavus with broad metatarsals and prominent heels", "mitochondrial encephalomyopathy" ]

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[ "lack of subcutaneous fat. The muscles and bones were clearly visible. He had mild dysmorphic features with high and arched eyebrows, a hairy forehead, triangular face, a slight upslant of palpebral fissures, down turned corners of the mouth, mild hypoplastic alae nasi, prominent pointed chin, deep incisura between tragus and antitragus providing a clear view into the external meatus", "small fingernails" ]

[ "First‐trimester combined test revealed a low risk for trisomies ( NT 1.1 mm ). The anomaly scan was performed at 20 weeks GA and showed no abnormalities. Transverse cerebellar diameter was normal at p50. At 25 + 5 weeks of gestation, she presented with signs of polyhydramnios ( uterine size that outpaced gestational age ) and premature contractions.", "Ultrasound showed polyhydramnios ( MVP 9.9 cm, AFI 27.5 cm ) with normal fluid‐filled stomach and mild dilatation of both lateral ventricles ( 11 mm ).", "enlarged cisterna magna ( 12 mm ) and a dysplastic and small cerebellum. The transcerebellar diameter measured 25.4 mm ( slightly below p3, with head circumference p50, Fig. 1 A ). Further intracranial assessment was not possible due to maternal habitus, fetal position, and uterine contractions. The myocardium was hypertrophic with a small perimembraneous VSD", "Two days later ( 26 + 0 ), she spontaneously delivered a boy of 835 g ( −0.5 SDS ), Apgar scores were 4/4/7 after 1.5 and 10 min, respectively.", "A few hours after birth, the neonate required mechanical ventilation and surfactant treatment for respiratory distress syndrome.", "the neonate died 2 days after birth", "polyhydramnios", "early presentation of polyhydramnios is most likely caused by hypotonia and diminished fetal movements", "polyhydramnios, causing premature delivery" ]

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[ "30‐year‐old" ]

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[ "FBXL4 ‐related encephalopathy" ]

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[ "intermittent vomiting, diarrhea, constipation, weight loss" ]

[ "The patient presented at age seven years with intermittent vomiting, diarrhea, constipation, weight loss and fatigue that has persisted for over 18 months", "multiple admissions for ketotic hypoglycemia and severe lactic acidosis" ]

[ "fatigue that has persisted for over 18 months" ]

[ "significant metabolic acidosis with low serum bicarbonate concentrations", "low serum glucose of 3.05 mmol / L ( 55 mg / dL ) and very low plasma l -carnitine ( total carnitine:7 μmol / L, reference range : 25–69 ). Serum creatine phosphokinase ( CK ) and transaminases were elevated and continued to increase as he clinically deteriorated, with CK peaking at 202 μkat / L ( 12,086 U / L ), AST at 341 U / L and ALT at 190 U / L.", "multiple admissions for ketotic hypoglycemia and severe lactic acidosis. Brain magnetic resonance imaging was normal, while brain magnetic resonance spectroscopy ( MRS ) showed lactate peaks in the left basal ganglion and lateral ventricle", "a low cerebrospinal fluid ( CSF ) 5 - methyltetrahydrofolate level", "urine organic acid profile was notable for elevations of lactate, ethylmalonate, 3 - methylglutaconate, and branched - chain ketoacids, suggestive of mitochondrial dysfunction. Cultured skin fibroblast testing was performed for suspected defects in fatty acid oxidation, pyruvate carboxylase ( EC 6.4.1.1 ), and pyruvate dehydrogenase complex ( EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4 ) with normal results. Analysis of acylcarnitines in cultured skin fibroblasts incubated with palmitic acid and l -carnitine ( in vitro probe assay ) showed marked elevations of long - chain species, suggestive of carnitine palmitoyltransferase II or carnitine – acylcarnitine translocase deficiency. CSF analysis showed mild elevation of lactate of 3.1 mmol / L ( < 2.8 ), and a low normal level of 5 - methyltetrahydrofolate. Transaminitis was initially attributed to a possible GSD; glycogen content was elevated in both liver ( 10 %; control range 3.3 + /− 1.7 % ) and muscle ( 3.0 %; control range 0.94 + /− 0.55 ). However, sequencing of PHKA1 and PHKG2 genes ( GSD IX ) and AGL gene ( GSD III ) was normal. Activities of debranching enzyme ( EC 2.4.1.25 GSD III ) and hepatic phosphorylase kinase ( GSD IX, EC 2.7.11.19 ) in the liver and muscle, and glucose-6 - phosphatase ( GSD Ia, EC 3.1.3.9 ) in the liver were also normal. Further evaluation for a suspected mitochondrial disorder revealed normal electron transporter chain ( ETC ) activity in cultured skin fibroblasts. Muscle histopathology demonstrated prominent granular red staining of the fibers with a trichrome stain and numerous mitochondria aggregates by electron microscopy, characteristic of a mitochondrial myopathy ( Fig. 1 ). ETC testing on frozen muscle revealed deficient complex III activity of 455 ( mean 1461, standard deviation 473 ); mtDNA sequencing of the muscle sample revealed a 9 basepair deletion with loss of 3 amino acids Leu - Ala - Thr ( m.15319_15327delCCTAGCAAC; p. Leu192_Thr194del, Fig. 2 ) in the MT - CYB gene encoding cytochrome b subunit of complex III, with > 90 % mutant load, confirming complex III deficiency. MtDNA sequencing in the liver and blood did not reveal the mutation, although low heteroplasmy for the mutation was detected in uncultured skin fibroblasts." ]

[ "ongoing cardiac evaluations to monitor for cardiomyopathy or rhythm disturbance have been normal." ]

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[ "improved exercise tolerance", "Previously confined to a wheel chair, he started to walk independently and actively" ]

[ "Ophthalmologic and audiologic exams were normal." ]

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[ "The patient presented at age seven years" ]

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[ "complex III deficiency" ]

[ "coenzyme Q10 , riboflavin , creatine monohydrate , alpha - lipoic acid , and medium chain triglyceride ( MCT ) oil was initiated , while continuing carnitine supplementation . Leucovorin was later added" ]

[ "height 182 cm, weight 80 kg" ]

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[ "with a previous history of divergence of the ocular bulbs with double vision since age 6y, bilateral ptosis since age 23y, which was surgically corrected at age 30y, ophthalmoparesis since at least age 27y, a syncope at age 30y, and anterocollis since at least age 40y.", "The family history was positive for diabetes ( grandmother from the mother ’s side ) and cardiac abnormalities ( mother )", "admitted for acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles", "A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency.", "He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y." ]

[ "bilateral ptosis since age 23y,", "ophthalmoparesis since at least age 27y,", "Electroneurography at age 27y revealed axonal polyneuropathy", "electroencephalography generalized poly - spike waves in the absence of seizures", "bilateral proximal weakness of the upper limbs, a winging scapula bilaterally, and reduced tendon reflexes", "Cerebrospinal fluid ( CSF ) investigations at age 40y revealed elevated protein ( 1008mg / l, n : 150 - 450mg / l ) exclusively", "Needle-(electromyography ) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations.", "mild weakness of the lower limbs ( M5-/M4 + )", "Upon supra - maximal stimulation of the phrenic nerve at age 41y no answer could be evoked", "needle - EMG of the rectus abdominis muscle revealed abnormal spontaneous activity", "was awake with normal oxygenation", "ptosis, ophthalmoparesis, weak head anteflexion and retroflexion ( M5- ), weakness of the upper limbs with distal predominance ( M4 to M5- ), proximal weakness of the lower limbs ( M5- ) absent tendon reflexes, generalized wasting, and stocking - type sensory disturbances", "Cerebral CT was normal.", "ophthalmoparesis since age 6y, ptosis since age 23y", "mitochondrial neuropathy, abnormal EEG, and elevated CSF - protein" ]

[ "muscle biopsy from the left deltoid muscle showing mild myopathic lesions with increased accumulation of intrafusal glycogen and lipid droplets", "Cerebrospinal fluid ( CSF ) investigations at age 40y revealed elevated protein ( 1008mg / l, n : 150 - 450mg / l ) exclusively", "Transthoracic echocardiography at age 40y revealed mild myocardial thickening", "Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm", "Lactate stress testing under 40W resulted in a lactate increase to 9.5mmol / l after 8 minutes", "Muscle biopsy from the right deltoid muscle at age 41y showed myopathic features, ragged - red fibers, regenerating fibers, increased number of lipid droplets, glycogen depositions, and some COX - negative fibers. Biochemical investigations of the muscle homogenate revealed a combined complex I+IV defect. The activity of the NADH - CoQ - oxidoreductase was 7.4 U / g NCP ( n, 15.8 - 42.84 U / g NCP ) and the activity of the cytochrome - c - oxidase 89 U / g NCP ( n, 112 - 351 U / g NCP ). Investigation for mtDNA deletions or insertions by long - range PCR was normal.", "Blood tests revealed hyponatriemia ( 129mmol / l, n : 135 - 150mmol / l ) and slight anemia", "Cerebral CT was normal.", "Blood gases normalized", "elevated CSF - protein", "Biochemical investigations revealed a combined complex I+IV defect" ]

[ "syncope at age 30y", "24h - ECG at age 30y disclosed an intermittent AV - block II", "Transthoracic echocardiography at age 40y revealed mild myocardial thickening", "no indication for heart failure" ]

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[ "abnormal respiratory pattern", "Radioscopy of the lungs did not reveal abnormal mobility of the diaphragm", "acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles", "hypercapnia due to muscular respiratory insufficiency", "The diaphragm was moving normally.", "respiratory insufficiency with hypercapnia recurred", "Under this regimen respiratory function further improved", "hypercapnia due to muscular respiratory insufficiency", "Respiratory insufficiency was attributed to mitochondrial myopathy affecting not only the extra - ocular and the axial muscles but also the shoulder girdle and respiratory muscles.", "muscular respiratory insufficiency" ]

[ "bilateral ptosis since age 23y,", "anterocollis since at least age 40y.", "bilateral proximal weakness of the upper limbs, a winging scapula bilaterally", "Needle-(electromyography ) EMG of the right anterior tibial muscle at age 40y showed neurogenic alterations", "mild weakness of the lower limbs ( M5-/M4 + )", "needle - EMG of the rectus abdominis muscle revealed abnormal spontaneous activity", "acute respiratory dysfunction in the absence of recent pulmonary infection or embolism with hypercapnia but normal oxygenation due to weakness of the respiratory muscles", "hypercapnia due to muscular respiratory insufficiency.", "ptosis, ophthalmoparesis, weak head anteflexion and retroflexion ( M5- ), weakness of the upper limbs with distal predominance ( M4 to M5- ), proximal weakness of the lower limbs ( M5- )", "generalized wasting,", "The diaphragm was moving normally.", "respiratory insufficiency with hypercapnia recurred", "he was able to sit with support during daytime", "Unsupported sitting was impossible due to affected truncal muscles.", "muscular respiratory insufficiency.", "ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y.", "mitochondrial myopathy affecting not only the extra - ocular and the axial muscles but also the shoulder girdle and respiratory muscles", "muscular respiratory insufficiency" ]

[ "divergence of the ocular bulbs with double vision since age 6y", "bilateral ptosis since age 23y,", "ophthalmoparesis since at least age 27y", "ptosis, ophthalmoparesis,", "ophthalmoparesis since age 6y, ptosis since age 23y," ]

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[ "45y", "45y" ]

[ "age 6y" ]

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[ "A 52 - year - old man presented at the National Hospital with 5 years history of progressive imbalance of gait, speech and memory impairment, and occasional urinary incontinence", "He has never smoked tobacco or taken alcohol", "His parents were first cousins from the Hausa ethnic group. His 78 - year - old father is alive and well. His 70 - year - old mother developed unsteady gait and dysphagia at age 55 years and is now bedridden and blind. His maternal aunt had died of a similar illness at age 39 years. Of his 12 siblings, all four sisters are alive and well, but five of eight brothers died. Three brothers died of unrelated causes, but one died at age 19 years following speech and swallowing difficulties while another one developed frequent falls, dementia, and blindness at age 27 years and died at 45 years. One brother is apparently healthy at age 54 years, but two others aged 42 and 43 years both suffer progressive imbalance of gait. The patient is married to one wife and has had seven children, of whom three have died. One son had frequent falls, seizures, abnormal speech, and blindness at age 8 years and died 3 years later. A daughter died of neonatal sepsis, while another daughter had unsteady gait and speech and swallowing difficulties at 2 years and died at 6 years.", "His mother and 42 - year - old brother both had visual impairment, ataxia, and sensory loss on examination" ]

[ "patient was oriented and scored 28/30 on the Mini - Mental State Examination Scale", "dysarthria and slow saccades on eye movement", "global hyperreflexia, bilateral ankle clonus, and extensor plantar responses", "Muscle power was 5/5 in all limbs", "glove - and - stocking sensory loss and bilateral cerebellar signs and scored 16/40 on the Scale for the Assessment and Rating of Ataxia", "brain magnetic resonance imaging revealed brainstem atrophy with normal spinal cord, cerebellum, and cerebral hemispheres," ]

[ "full blood count, serum chemistry, fasting glucose, lipid profile, thyroid function tests, serum Vitamins E and B12 levels, and electrocardiogram were all normal", "brain magnetic resonance imaging revealed brainstem atrophy with normal spinal cord, cerebellum, and cerebral hemispheres", "Each of the three samples tested showed expansion mutations of 39 repeats at the SCA7 ( ATXN7 ) gene locus, where one normal allele and one fully expanded allele ( 10/39 ) were observed. '" ]

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[ "Muscle power was 5/5 in all limbs." ]

[ "and slow saccades on eye movement. Visual acuity was 6/18 in both eyes, and fundoscopy showed bilateral peripapillary atrophy" ]

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[ "52 - year - old" ]

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[ "SCA7" ]

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[ "nausea," ]

[ "A 48 - year - old woman of Palestine origin presented to a local hospital with subacute onset of confusion and word - finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness.", "Her medical history was significant for essential hypertension, poorly controlled type 2 diabetes mellitus, and bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years", "moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity.", "On day 4 of hospitalization, the patient reported feeling better, and her family took her home against medical advice. She then suffered 2 generalized tonic – clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night.", "A detailed 3 - generation family history revealed no known neurologic, muscular, cardiac, or vision problems" ]

[ "presented to a local hospital with subacute onset of confusion and word - finding difficulties. Her symptoms had started 2 weeks earlier with a headache, nausea, and dizziness.", "her symptoms initially stabilized, but in the following week, the patient 's confusion worsened, and she developed clumsiness and stiffness of her right arm. At that point, she was referred to our institution for further evaluation. On admission, she had moderate expressive aphasia, mild dysarthria, and apraxia with paratonia of her right upper extremity", "She then suffered 2 generalized tonic – clonic seizures associated with severe headache and blurred vision, and she was readmitted to our institution the same night. Continuous electroencephalogram showed left hemispheric slowing and frequent seizures originating from the left occipital lobe.", "her cognition including language and activities of daily living had greatly improved." ]

[ "Computed tomography ( CT ) revealed a hypodense lesion within the left temporal lobe ( edema ) involving gray matter and white matter ( Fig. 1 ). Magnetic resonance imaging ( MRI ) demonstrated left temporal lobe diffusion signal abnormality and fluid - attenuated inversion recovery ( FLAIR ) hyperintensity predominantly involving the cortex, with cortical and leptomeningeal contrast enhancement. The apparent diffusion coefficient ( ADC ) map showed preserved, isointense signal in the temporal cortex ( Fig. 2 ). The ventricular system and remaining parenchyma were grossly normal. Normal patent vessels without stenosis were seen on MR angiogram ( Fig. 3 )", "Imaging showed partial resolution of the left temporal lobe lesion, and new cortical diffusion weighted imaging abnormality in the left temporal and occipital lobes with corresponding FLAIR hyperintensity ( Fig. 2 ). Normal ADC signal and postcontrast leptomeningeal enhancement were similarly seen in these regions. Positron emission tomography ( PET ) showed no evidence of malignancy but demonstrated reduced metabolic activity in the regions of signal abnormality with adjacent metabolic hyperactivity involving the left superior parietal and medial occipital lobes in a gyriform distribution. Lumbar puncture ruled out infection but was significant for elevated lactate to 5.1 mmol / L. Serum lactate was elevated to 4.6 mmol / L. Serum inflammatory markers ( dsDNA, anti - Hu, anti - Ri, anti - Yo, SS - A, SS - B, C3, C4 ) were normal.", "Subsequent MRI demonstrated extension of the occipital lesion to involve more of the parietal and occipital lobes ( Fig. 4 ). MR spectroscopy showed elevated lactate peak at 1.3 ppm diffusely throughout the brain", "Genetic testing of patient 's serum confirmed m.3243 A→G mutation ( heteroplasmy 22 % ) in the MT - TL1 gene that encodes leucine transfer RNA, consistent with MELAS syndrome" ]

[ "essential hypertension" ]

[ "poorly controlled type 2 diabetes mellitus" ]

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[ "dizziness", "bilateral hearing loss of unknown etiology requiring hearing aids since age 46 years", "blurred vision," ]

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[ "48 - year - old" ]

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[ "MELAS syndrome" ]

[ "high - dose intravenous arginine then oral citrulline at 0.5 mg / kg" ]

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[ "vomiting" ]

[ "The patient was a 41 - year - old man who had experienced generalized convulsions, insomnia, and depression since 20 years of age", "He had been diagnosed with ischemic stroke at 33 years of age and epileptic seizure with epileptic encephalopathy at 37 years of age. He had no other systemic signs of mitochondrial disorder, such as short stature, diabetes mellitus, deafness or heart failure.", "His family history was not remarkable", "He developed myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age", "Three months later, he was admitted to our hospital due to impaired consciousness and vomiting", "his family had no clinical symptoms suggestive of mitochondrial diseases", "Over a two - month period, he experienced two stroke - like episodes with simple partial seizure and vomiting. Each time the stroke - like episodes ended within four days" ]

[ "generalized convulsions, insomnia, and depression", "ischemic stroke at 33 years of age", "epileptic seizure with epileptic encephalopathy at 37 years of age.", "myoclonus in the distal extremities, gait disturbance, and dysarthria at 41 years of age.", "impaired consciousness", "gaze nystagmus, cerebellar ataxia, and myoclonic movement in his distal extremities", "no ophthalmoplegia, hearing loss, or muscle weakness", "His mini - mental status examination score was 15/30, and his frontal assessment battery score was 5/18", "The cerebrospinal fluid lactate ( 34.8 mg / dL ) and pyruvic acid ( 1.6 mg / dL ) levels were elevated.", "Brain magnetic resonance imaging ( MRI ) showed bilateral cortical and subcortical high - intensity lesions on T2 - weighted imaging ( T2WI ) and fluid attenuated inversion recovery ( FLAIR ), distributed bilaterally and almost symmetrically. Bilateral red nuclei, mesencephalic tectum, vermis and cerebellar flocculus were also involved ( Fig. 1A and C ). Some of the cortical and subcortical lesions gave a high signal on diffusion - weighted imaging ( DWI ) ( Fig. 1B ). These lesions appeared as high or iso signal intensity on the apparent diffusion coefficient ( ADC ) map. Two weeks later, the high signal on DWI had diminished, and four weeks later, the high signal on T2WI and FLAIR had diminished ( Fig. 2 ). 1 H - MRS revealed elevated lactate concentrations in the lesions ( Fig. 1D ).", "99 m Tc - Ethylcysteinate dimer single photon emission computed tomography ( SPECT ) imaging revealed bilateral multifocal increase of perfusion in the MRI lesions", "two stroke - like episodes with simple partial seizure and vomiting", "Each time the stroke - like episodes ended within four days", "epileptic seizure", "His higher brain dysfunction and myoclonus worsened with each stroke - like episode" ]

[ "routine blood tests including blood sugar and autoimmune antibodies were normal. A laboratory examination showed slightly increased serum pyruvic acid levels ( 1.2 mg / dL ), but his serum lactate levels were normal ( 14.2 mg / dL ). The cerebrospinal fluid lactate ( 34.8 mg / dL ) and pyruvic acid ( 1.6 mg / dL ) levels were elevated. Electrocardiogram and echocardiogram were normal. Brain magnetic resonance imaging ( MRI ) showed bilateral cortical and subcortical high - intensity lesions on T2 - weighted imaging ( T2WI ) and fluid attenuated inversion recovery ( FLAIR ), distributed bilaterally and almost symmetrically. Bilateral red nuclei, mesencephalic tectum, vermis and cerebellar flocculus were also involved ( Fig. 1A and C ). Some of the cortical and subcortical lesions gave a high signal on diffusion - weighted imaging ( DWI ) ( Fig. 1B ). These lesions appeared as high or iso signal intensity on the apparent diffusion coefficient ( ADC ) map. Two weeks later, the high signal on DWI had diminished, and four weeks later, the high signal on T2WI and FLAIR had diminished ( Fig. 2 ). 1 H - MRS revealed elevated lactate concentrations in the lesions ( Fig. 1D ). 99 m Tc - Ethylcysteinate dimer single photon emission computed tomography ( SPECT ) imaging revealed bilateral multifocal increase of perfusion in the MRI lesions", "histopathological study of the biopsied right biceps branchii muscle revealed mild variation in the fiber size, measuring from 30 to 90 microns in diameter, which was thought to be a non - specific change. No necrotic or regenerating fibers were seen. On modified Gomori - trichrome stain, ragged red fibers ( RRFs ) were not observed. Succinate dehydrogenase ( SDH ) stain revealed no strongly SDH - reactive blood vessels. Cytochrome c oxidase staining revealed no abnormalities ( Fig. 1F ). However, the complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T > C mutation, with a level of mutant heteroplasmy of 69.5 %, in the mitochondrial complex I subunit gene, MT - ND3" ]

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[ "gaze nystagmus", "no ophthalmoplegia, hearing loss" ]

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[ "41 - year - old" ]

[ "20 years of age" ]

[ "MELAS - like encephalopathy" ]

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[ "157 cm in height and 45 kg in weight", "normal body temperature of 36.8 ° C, a hypotension of 90/56 mm Hg and pulse at 72 beats per minute." ]

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[ "The patient was a 37 - year - old female, of 157 cm in height and 45 kg in weight. She was transferred to our department from a local hospital due to psychiatric features ( both agitated behavior and auditory hallucinations ), alexia and apraxia that had begun 10 days ago, followed by disorientation and generalized tonic - clonic seizures.", "She had a long history of episodic migraine - like headaches and progressive bilateral hearing loss for 3 years." ]

[ "psychiatric features ( both agitated behavior and auditory hallucinations ), alexia and apraxia that had begun 10 days ago, followed by disorientation and generalized tonic - clonic seizures. She had a long history of episodic migraine - like headaches", "An electroencephalogram was performed on day 7 and displayed bilateral slow wave activities." ]

[ "high anion gap metabolic acidosis with elevated levels of lactate and pyruvate. Serum levels of thyroid - stimulating hormone ( TSH ) and free thyroxine ( FT4 ) were decreased. Her TSH level was low at 0.26 mU / L ( normal range 0.35–5.5 mU / L ), and FT4 concentration was 7.56 pmol / L ( normal range 10.2–31 pmol / L ). Both serum free and total triiodothyronine ( FT3 and TT3 ) were significantly lower than normal range. FT3 concentration was 2.28 pmol / L ( normal range 3.5–6.5 pmol / L ), and TT3 concentration was 0.6 nmol / L ( normal range 1.2–3.4 nmol / L ). Moreover, elevated titers of serum anti - thyroglobulin and anti - thyroid microsomal antibodies were detected. Cerebral spinal fluid ( CSF ) studies were normal for cell counts and biochemistry, and negative for culture. CSF IgG index was 0.48 ( normal range ≤ 0.7 ), and oligoclonal bands ( OB ) was negative. Computed tomography ( CT ) scan showed lesions of hypodense in the left temporal and parietal lobe, with brainstem and cerebellar atrophy ( Fig. 1 A ). No evidence of subarachnoid or intracerebral hemorrhage. Vascular imaging of the cervical and cerebral arteries by CT angiography excluded the possibility of cerebrovascular disease ( Fig. 1 B ). However, CT images were not conclusive to differentiate between the infectious or metabolic lesion. On day 5, brain magnetic resonance imaging MRI ( 3.0 T ) revealed a hypointensity lesion in the left temporal - parietal lobe on T1 weighted image ( Fig. 2 A ), and increased signal intensity in the same region on FLAIR sequences ( Fig. 2 B ) with a clearly restricted diffusion ( Fig. 2 C ). The signal intensity on ADC sequence was mildly reduced ( Fig. 2 D ). No obvious enhancement was found on Gd - DTPA enhanced images ( Fig. 2 E ). MR spectroscopy was carried out as well. Compared to the ipsilateral normally appearing area ( Fig. 2 F ), there was a significantly elevated lactate peak at 1.3 ppm in region of interest ( ROI ) with decreased NAA spectrum and reduced NAA / Cr ratio ( Fig. 2 G ). The change of the spectrum reflected the severity of metabolic disorders, suggesting the local accumulation of lactic acid and disturbance of hypoxic processes. Fig. 1 CT scan showed lesions of hypodense in the left temporal and parietal lobe ( Panel A ). Three - dimensional reconstruction of CT vessel images ( Panel B ). Fig. 1 Fig. 2 Brain MRI ( 3.0 T ) revealed a hypointense lesion in the left temporal and parietal lobe on T1 ( Panel A ), and increased signal intensity in the same region on Flair ( Panel A ) image with a clearly restricted diffusion ( Panel C ). The signal intensity on ADC sequence is mildly reduced ( Panel D ). No obvious enhancement was found on Gd - DTPA enhanced images ( Panel E ). Compared to the ipsilateral normally appearing area ( Panel F ), MR spectroscopy presented a significantly elevated lactate peak at 1.3 ppm in region of interest ( ROI )", "mitochondrial DNA ( mtDNA ) mutation at A3242 G point" ]

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[ "progressive bilateral hearing loss", "Brainstem auditory evoked potential ( BAEP ) showed the bilateral sensorineural hearing loss." ]

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[ "37 - year - old" ]

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[ "The final diagnosis of MELAS syndrome was confirmed by genetic analysis ." ]

[ "L - arginine , phenobarbital , co - enzyme Q and levothyroxine substitution therapy ." ]

[ "A complete blood count and a complete biochemistry panel were performed, and all of the results were within normal limits" ]

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[ "A 7 - month - old, entire female, domestic shorthair cat was referred to our behavioural service owing to house soiling and a play - related problem. The owners ’ complaints were that the cat had never used the litter tray, and it did not know how to play", "After 3 months, the cat was referred to the neurology service again, in status epilepticus.", "After 2 years of treatment and a progressive worsening, the cat was euthanased." ]

[ "house soiling and a play - related problem.", "did not know how to play.", "the cat did not understand the body language of other cats and commonly crashed into other cats or people. It also ‘ tried to bite, catch and scratch the air ’ when playing. It did not find balls or other toys when the owners threw them to the cat to play. The rest of the cat ’s behavioural history was unremarkable", "moderate and hypermetric ataxic gait, and a bilateral lack of menace response", "based on the behaviours at home described by the owners ( the inability to find some toys, and the behaviour of ‘ scratching and biting the air ’ ), some degree of visual impairment was suspected but not confirmed", "The cat did not crash with objects either at home or at the consultation room", "brain magnetic resonance imaging ( MRI; 0.2 T ) and cerebrospinal fluid analysis showed no abnormalities.", "suggests that there was a learning impairment during the acquisition of habits but not a total lack of learning capability.", "status epilepticus", "lack of bilateral menace response and cerebellar ataxic gait", "progressive gait deficits over the previous month and compulsive running episodes with a partially impaired mental status ( probably seizure activity )", "seizures reappeared after 2 months with 1–2 episodes every 15 days each lasting < 2 mins", "No gross lesions were found, and based on the CNS histological lesions shown in Figures 1 – 4, a diagnosis of spongiform polioencephalomyelopathy was made. The spongiform degeneration of the grey matter was extensively distributed in the whole CNS." ]

[ "A complete blood count and a complete biochemistry panel were performed, and all of the results were within normal limits. The feline immunodeficiency virus / feline leukaemia virus test was negative.", "A thorax radiograph, abdominal ultrasound, brain magnetic resonance imaging ( MRI; 0.2 T ) and cerebrospinal fluid analysis showed no abnormalities.", "Amino acids, organic acids, carbohydrates, nitroprusside, ketone and mucopolysaccharide concentrations were analysed, as was α - mannosidase, β - mannosidase, fucosidase and hexosaminidase A and B activity. All of these were within normal limits.", "No gross lesions were found, and based on the CNS histological lesions shown in Figures 1 – 4, a diagnosis of spongiform polioencephalomyelopathy was made. The spongiform degeneration of the grey matter was extensively distributed in the whole CNS.", "PrPsc inmunohistochemistry assay was performed, and the results were negative" ]

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[ "bilateral carpal valgus" ]

[ "No ophthalmological abnormalities were detected", "based on the behaviours at home described by the owners ( the inability to find some toys, and the behaviour of ‘ scratching and biting the air ’ ), some degree of visual impairment was suspected but not confirmed", "visible suture line in the posterior capsule of both crystalline lenses were also detected" ]

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[ "7 - month - old" ]

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[ "congenital spongiform polioencephalomyelopathy ( CSP ) was diagnosed postmortem" ]

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[ "poor weight gain with swallowing dysfunction and significant reflux disease" ]

[ "This boy was born to nonconsanguineous Chinese parents. He was born at term, weighed 3100 g with good Apgar scores. He had global developmental delay at 7 months of age with severe head lag and generalized hypotonia.", "He had poor weight gain with swallowing dysfunction and significant reflux disease", "He started having orofacial and limb dyskinesias at 1.5 years of age and subsequently developed refractory multifocal epilepsy at 3 years of age", "He developed central and obstructive sleep apneas at 3.5 years of age", "Parents were carriers of the mutation", "The parents ’ first child was diagnosed with steroid - resistant nephrotic syndrome at 18 months of age requiring tacrolimus treatment. Their second pregnancy was terminated at 22 weeks ’ gestation due to antenatal diagnosis of Ebstein ’s anomaly and multiple valvular abnormalities." ]

[ "He had global developmental delay at 7 months of age with severe head lag and generalized hypotonia", "brachycephalic", "swallowing dysfunction", "started having orofacial and limb dyskinesias at 1.5 years", "refractory multifocal epilepsy at 3 years of age", "Electroencephalogram showed focal and diffuse slowing consistent with background encephalopathic state, with frequent multifocal epileptiform discharges bilaterally", "magnetic resonance imaging brain scan and chromosomal microarray at 8 months of age, which was normal.", "has generalized dystonia, and is mainly chair - bound. He has intermittent eye contact and minimal vocalization" ]

[ "magnetic resonance imaging brain scan and chromosomal microarray at 8 months of age, which was normal.", "Whole - exome sequencing and direct sequencing confirmed that he harbored compound heterozygous missense mutations c.3130C > T ( p. Arg1044Cys ), c.3430C > T ( p. Arg1144Cys ), and c.4078G > A ( p. Ala1360Thr ) in the LRPPRC gene", "His muscle biopsy showed normal muscle architecture with no “ ragged - red ” fibers, necrotic fibers, or regenerating fibers seen. Cytochrome c - oxidase was positive in most of the fibers. There were no light microscopic or ultrastructural features to support mitochondrial myopathy. Respiratory chain enzymes in skeletal muscle were diagnostic for complex IV defect", "His baseline lactates ranged from 1.5 to 3.6 mmol / L with mild intermittent metabolic acidosis. However, there were no episodes of acute ketosis, glycemic derangements, or any acute stroke - like episodes" ]

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[ "central and obstructive sleep apneas at 3.5 years of age" ]

[ "brachycephalic" ]

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[ "hypopigmented hair" ]

[ "He was born at term, weighed 3100 g with good Apgar scores." ]

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[ "5 years of age" ]

[ "7 months of age" ]

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[ "' On physical examination, the height and weight of the patient were 154 cm and 56 kg, respectively. Vital signs were normal" ]

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[ "A 52 - year - old female presented with a sudden onset of right - sided numbness and weakness that was accompanied by a left temporal cluster - like headache. No fever or prodromal infection was found at disease onset.", "Two months later, the patient was readmitted for subacute cognitive impairment. She was unable to identify and communicate with family members; she also had difficulty understanding questions or instructions and instead responded by repeating the word \" nothing \". During hospitalization, a secondary generalized seizure occurred, initially with eyes gazing to the right and then convulsion developing, which lasted for approximately 10 s before self - alleviation", "At 3 mo after her second admission, the patient was experiencing involuntary movement in her left limbs, with repetitive flexion / extension.", "The family and personal history was unremarkable.", "After admission, she complained of discomfort and tingling in the right leg, after which a generalized tonic - clonic seizure for 3 min occurred", "52 - year - old woman with recurrent stroke - like episodes" ]

[ "sudden onset of right - sided numbness and weakness that was accompanied by a left temporal cluster - like headache.", "Two months later, the patient was readmitted for subacute cognitive impairment. She was unable to identify and communicate with family members; she also had difficulty understanding questions or instructions and instead responded by repeating the word \" nothing \". During hospitalization, a secondary generalized seizure occurred, initially with eyes gazing to the right and then convulsion developing, which lasted for approximately 10 s before self - alleviation. Neurological examination suggested transcortical sensory aphasia, with fully covered limb strength", "At 3 mo after her second admission, the patient was experiencing involuntary movement in her left limbs, with repetitive flexion / extension.", "Neurological examination showed intact mental status, with normal speech and comprehension. Mild 4/5 right - sided hemiparesis was present with normal tone in both the arm and leg, though no other focal neurological deficits were found. After admission, she complained of discomfort and tingling in the right leg, after which a generalized tonic - clonic seizure for 3 min occurred", "recurrent stroke - like episodes", "sudden onset of right - sided hemiparesis and hemilateral sensory disturbance accompanied by a left temporal cluster - like headache and later developed epilepsy during hospitalization" ]

[ "MRI demonstrated a lamellar left parietal lobe lesion predominantly involving the cortex, with hyperintensity on both diffusion - weighted imaging and fluid - attenuated inversion recovery ( Figure 1 ). The apparent diffusion coefficient map revealed a preserved, isointense signal. No abnormalities were found by susceptibility weighted imaging or magnetic resonance angiography and venography ( Figure 1 ). Due to the stroke - like onset pattern and MRI features, further thrombophilia screening was performed and showed decreased protein S activity.", "Blood tests and CSF examination were normal; INR was 2.21. On repeated MRI, new lesions were identified in the left temporal lobe and were also detected 10 days later in the right temporal lobe on radiological follow - up ( Figures 1 and 2 ). Although the MRI signal characteristics are consistent with the initial findings, the original lesion in the left parietal lobe had been alleviated, with cortical atrophy. We further conducted magnetic resonance spectroscopy ( MRS ), which revealed markedly elevated lactate ( Lac ) concentrations in the regions of interest in the left temporal lesion", "MRI scan showed a hyperintense signal abnormality in the right parietal lobe ( Figure 2 ). Brachial biceps biopsy was performed. Histopathology revealed no abnormalities, and no necrotic or regenerating fibers were observed; ragged - red fibers and intense succinate dehydrogenase activity were not detected. Nonetheless, complete sequencing of mitochondrial DNA samples extracted from the biopsied muscle revealed a heteroplasmic m.10158T > C mutation, with a heteroplasmy level of 69.6 %, in the mitochondrial complex I subunit gene MT - ND3. In contrast, this mutation was not found in her peripheral blood cells.", "Brain magnetic resonance imaging revealed variable lesions involving multiple cortical and subcortical regions.", "Laboratory tests, including D - dimer, lactic acid, and serum autoantibody levels, as well as thyroid function and tumor markers indicated no apparent abnormalities. Glucose tolerance and lactic acid movement tolerance tests were normal. A lumbar puncture was performed, and her open intracranial pressure was 180 mm H 2 O. Cerebrospinal fluid ( CSF ) testing showed that cell counts and protein, glucose, chloride, monoclonal antibody, adenosine deaminase, and lactate dehydrogenas levels were within normal ranges." ]

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[ "lack of symptoms of muscle weakness or pain", "no other signs suggestive of myopathy" ]

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[ "52 - year - old" ]

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[ "m.10158T > C mutation in the MT - ND3 gene" ]

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[ "On admission to the ICU, the vital signs were as follows : body temperature, 39 ° C; blood pressure, 150/80 mmHg; heart rate, 150 b.p.m.; respiratory rate, 30 breaths / min; and SpO2, 99 % ( FiO 2 40 % )" ]

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[ "A 24‐year‐old woman who had been diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes was admitted to our hospital with impaired consciousness and myoclonus." ]

[ "mildly impaired consciousness and myoclonus in the extremities", "myoclonic movement in the extremities, mandible, and trunk", "Brain magnetic resonance imaging showed bilateral high‐intensity lesions in the temporal and parietal lobes of the cortical and subcortical areas in T2 weighted imaging", "impaired consciousness and myoclonus persisted for 2 weeks", "brain magnetic resonance imaging again, which revealed high‐intensity lesions in the right cortical temporal lobe, and arterial spin labeling showed increased blood flow in the bilateral frontal and temporal cortex.", "Electroencephalography revealed high‐amplitude slow and spiked waves", "non‐convulsive status epilepticus", "impaired consciousness and myoclonus", "non‐convulsive status epilepticus" ]

[ "Genetic testing revealed a 3271 T > C transition in the MT‐TL1 gene", "A laboratory examination showed increased serum pyruvic acid ( 2.1 mg / dL ) and lactate ( 75 mg / dL )", "Brain magnetic resonance imaging showed bilateral high‐intensity lesions in the temporal and parietal lobes of the cortical and subcortical areas in T2 weighted imaging", "brain magnetic resonance imaging again, which revealed high‐intensity lesions in the right cortical temporal lobe, and arterial spin labeling showed increased blood flow in the bilateral frontal and temporal cortex", "arterial blood gas revealed metabolic acidosis ( pH 7.261, pCO 2 33.0 mmHg, HCO 3 - 14.4 mmol / L, and lactate 99 mg / dL ). Creatinine kinase was elevated at 20,999 U / L.", "Laboratory findings showed metabolic acidosis ( lactic acid, 99 mg / dL; pyruvic acid, 0.92 mg / dL ), creatinine kinase 29,560 U / L, and myoglobin 9,845 ng / mL.", "metabolic acidosis and creatinine kinase gradually decreased after reaching 59,000 IU / L", "Arterial blood gas revealed metabolic acidosis, and creatinine kinase was elevated." ]

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[ "urine appeared brown", "PRIS" ]

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[ "Muscle weakness was detected in the upper and lower limbs bilaterally", "urine appeared brown", "PRIS" ]

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[ "24‐year‐old", "24‐year‐old" ]

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[ "diagnosed with MELAS at 21 years of age . Genetic testing revealed a 3271 T > C transition in the MT‐TL1 gene , clinically confirming the diagnosis of MELAS", "diagnosed with mitochondrial myopathy , encephalopathy , lactic acidosis , and stroke‐like episodes" ]

[ "L‐arginine , coenzyme Q10 , and L‐carnitine aimed at supporting mitochondrial energy production were given", "We continued coenzyme Q10 , L‐carnitine , and L‐arginine for mitochondrial support for MELAS" ]

[ "normal vital signs and a body - mass index of 25 ( height : 1.65 m, weight : 68 kg )." ]

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[ "A 50 - year - old male with a history of MERRF syndrome was found to have serum prostate specific antigen of 9.45 ng per milliliter on routine screening. His urological history was significant for mild to moderate voiding dysfunction consisting of hesitancy and nocturia, with an International Prostate Symptom Score of 14/35. There was no erectile dysfunction with a normal International Index of Erectile Function score ( 24/25 ).", "past medical history was significant for a history of hypertension and hypercholesterolemia", "surgical history included a tonsillectomy as a child and plastic surgery to remove neck lipomas", "family history was positive for lung and liver cancer in his mother" ]

[ "did not include cognitive impairment nor seizures", "neurological examination was normal except for mild muscle weakness at the end of the day" ]

[ "serum prostate specific antigen of 9.45 ng per milliliter on routine screening.", "urinalysis was negative for pyuria or microscopic hematuria", "common MERRF mitochondrial DNA mutation ( A8344 G ) in his blood", "prostate biopsy revealing grade group 2 adenocarcinoma ( Gleason score 3 + 4 = 7 ) at the left mid for 9 mm ( mm. ) and right base for 5.5 mm., and grade group 1 ( Gleason score 3 + 3 = 6 ) at the left base for 9 mm. Perineural invasion was present", "His transrectal prostate ultrasound showed a prostate volume of 28.9 cc but no hypoechoic nodules. His calculated PSA density was 0.32 ng / ml / cc.", "His prostatectomy pathology was grade group 2, pathologic stage T2 with negative margins and lymph nodes.", "PSA was less than 0.1. ng / ml", "PSA remains less than 0.1 ng / ml. ' }" ]

[ "hypertension and hypercholesterolemia" ]

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[ "serum prostate specific antigen of 9.45 ng per milliliter on routine screening.", "mild to moderate voiding dysfunction consisting of hesitancy and nocturia, with an International Prostate Symptom Score of 14/35", "no erectile dysfunction with a normal International Index of Erectile Function score ( 24/25 ).", "normal external genitalia", "soft prostate with good lateral definition bilaterally and an estimated volume of 30 cubic centimeters", "His transrectal prostate ultrasound showed a prostate volume of 28.9 cc but no hypoechoic nodules. His calculated PSA density was 0.32 ng / ml / cc.", "high PSA density, moderate voiding dysfunction, and grade group 2 with significant involvement ( 9 mm. 5.5 mm., 9 mm. )", "His prostatectomy pathology was grade group 2, pathologic stage T2 with negative margins and lymph nodes.", "PSA was less than 0.1. ng / ml.", "After 6 months, the patient could achieve intercourse with the aid of vardenafil on - demand with an International Index of Erectile function of 20/25", "At last follow - up 52 months after surgery, the patient continues to be continent, has satisfactory sexual function using daily tadalafil, and his PSA remains less than 0.1 ng / ml. '" ]

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[ "exercise intolerance and mild muscle atrophy", "mild muscle weakness at the end of the day." ]

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[ "symmetric lipomas in his cervical region", "multiple symmetric lipomatosis", "large, painless, symmetrical cervical lipomas", "cervical lipomas", "neck lipomas" ]

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[ "50 - year - old" ]

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[ "common MERRF mitochondrial DNA mutation ( A8344 G )" ]

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[ "The patient was a 22 - year - old woman with a clinical history of recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure", "one of her father 's cousins had a para - aortic pheochromocytoma, an incidental finding in the emergency department due to abdominal pain" ]

[ "headache." ]

[ "Results of transthoracic echocardiography and renal Doppler imaging were normal, and plasma and urine metanephrine levels were within normal limits", "New transthoracic echocardiography showed high velocities in the pulmonary artery and a mass with intermediate echogenicity located at the base of the heart in close relation to the aorta and the pulmonary artery, extending into the left atrioventricular groove", "Free metanephrines in plasma ( noradrenaline 4,886.67 pg / mL ) and urine ( noradrenaline 1,426.9 μg/24 h ) were high.", "Transthoracic echocardiography. Shown is a mass ( white arrow ) with intermediate echogenicity in relation to the great vessels.", "cardiac magnetic resonance was performed and showed a middle mediastinal mass located in the left atrioventricular groove, extending posteriorly to the left atrial roof and almost surrounding the pulmonary artery anteriorly. The mass was closely associated with the aortic root, but the emergence and path of the left coronary artery and its branches were not adequately visualized ( Figure 2 ). Tissue characterization sequences showed a mass with a heterogeneous appearance on T2 - weighted sequences and slightly hyperintense on T1 - weighted and T2 with fat saturation sequences ( Figure 2 ). Important mass vascularization was demonstrated with the perfusion sequence, which showed rapid uptake of contrast shortly after its administration. We also found focal late gadolinium enhancement at the periphery of the mass, with no enhancement at its center, a finding that was considered highly suggestive of a paraganglioma", "Fluorine-18 fluorodeoxyglucose positron emission tomography was also performed, demonstrating a highly metabolic mass", "Cardiac magnetic resonance. ( 1 ) Coronal : isointense mass in relation to the left atrial roof. ( 2 ) Two - chamber longitudinal : isointense mass in the left atrioventricular groove. ( 3,4 ) Axial : mass in relation to the aortic root and the pulmonary artery.", "Cardiac magnetic resonance. Delayed enhancement. Focal deposit of gadolinium in the periphery of the mass.", "Positron emission tomography with 18F - fluorodeoxyglucose ( 10 mCi ). Hypermetabolic mass in the middle mediastinum", "coronary angiotomography was performed. The mass was found to surround the left main coronary artery, the proximal segment of the left anterior descending coronary artery, the circumflex coronary artery, and two septal arteries, as well as the great cardiac vein", "Figure 5 Coronary computed tomography. Mass surrounding the left main coronary artery and the proximal segment of the anterior descending and the circumflex coronary arteries. Figure 6 Coronary computed tomography. Mass surrounding the pulmonary artery. Figure 7 Coronary computed tomography. Mass located in the left atrioventricular groove. Figure 8 Coronary arteriography. Mass irrigated by multiple small vessels arising from the anterior descending coronary artery.", "Follow - up echocardiography showed that systolic function was moderately affected, with an ejection fraction of 35 % and diffuse hypokinesia, which was more pronounced in the anterior descending coronary artery territory", "new coronary angiography was performed, ruling out saphenous bridge compromise", "Further follow - up echocardiography showed improvement in systolic function, with an ejection fraction of 55 % and preserved contractility of all segments except the basal segment of the anterior septum, which continued to be akinetic. There was also moderate pericardial effusion without increased intrapericardial pressure", "Figure 10 Coronary angiography. Saphenous bridge patent to the anterior descending artery, without lesions. Figure 11 Transthoracic echocardiography. ( 1 ) Parasternal view in diastole : pericardial effusion. ( 2 ) Parasternal view in systole : akinesia of the basal anteroseptal segment", "pathology report of the surgical specimen described round and oval cells in an organoid pattern with fine chromatin nuclei and degenerative focal atypia", "Round and oval cells, arranged in an organoid pattern, with degenerative focal atypia." ]

[ "cardiac paraganglioma with left coronary artery involvement.", "recurrent episodes of palpitations, diaphoresis, and headache. She was found to have high blood pressure and, because of her age, several studies were done looking for secondary hypertension", "Ambulatory blood pressure monitoring found severe hypertension, and the patient started treatment with angiotensin receptor blockers. After 2 years, she continued to have the same symptoms, but at this time, a mesocardial systolic murmur with back irradiation was found on auscultation", "follow - up echocardiography showed improvement in systolic function, with an ejection fraction of 55 % and preserved contractility of all segments except the basal segment of the anterior septum, which continued to be akinetic. There was also moderate pericardial effusion without increased intrapericardial pressure" ]

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[ "22 - year - old" ]

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[ "The genetic study showed a succinate dehydrogenase subunit B mutation ." ]

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[ "A 57 - year - old woman presented with a history of multiple painful subcutaneous masses especially around her neck but also bilaterally on her upper arms, back, abdomen, and upper legs. The patient was referred from the neurology department for management of these painful masses, which were obstructing her ability to breath and sleep, forcing her to require home oxygen and a wheelchair for ambulation. She could not lie on her back because of the prominence of the lipomatosis behind her neck and upper back", "Our patient reported a history of myoclonus epilepsy with ragged red fibers ( MERRF ) syndrome with symptoms including cardiomyopathy, peripheral neuropathy, ataxia, muscle weakness, and myoclonus", "She reported multiple family members having MERRF syndrome including her mother, maternal grandmother, maternal great grandmother, sisters, brothers, her sons, and nephews with variable presentations and lipomas" ]

[ "wheelchair for ambulation.", "peripheral neuropathy, ataxia,", "myoclonus" ]

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[ "cardiomyopathy" ]

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[ "these painful masses, which were obstructing her ability to breath and sleep" ]

[ "muscle weakness," ]

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[ "multiple painful subcutaneous masses especially around her neck but also bilaterally on her upper arms, back, abdomen, and upper legs", "She could not lie on her back because of the prominence of the lipomatosis behind her neck and upper back.", "Multiple symmetric large, variably sized tender masses were easily apparent and palpable around her neck, upper back, upper lateral arms, mid and lower back, lower abdomen, and upper thighs", "symmetric supraclavicular lipomatosis", "Upper back buffalo hump lipomatosis", "Symmetric lipomatosis of upper arms." ]

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[ "57 - year - old" ]

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[ "myoclonus epilepsy with ragged red fibers ( MERRF )" ]

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[ "The highest temperature was 37.8 ° C" ]

[ "vomiting 4 to 5 times on the same day," ]

[ "A 12 - year - old boy was admitted to Shaoxing People 's Hospital because there is a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking after treatment of unexplained fever and somnolence" ]

[ "a reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking", "and somnolence.", "insufficient spirits.", "His electroencephalogram showed clear increase of 4–5c / s theta waves, 2–3c / s delta waves, with a small amount of sharp waves", "His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right ( Fig. 1 A ). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS", "In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range", "able to walk and talk slowly with improved writing skills and no stroke - like episodes", "neurological examination was negative", "reduction in the volume of speech, dysphonia, unable to write, recognize words, and unable to wear clothes, accompanied by unstable walking", "somnolence." ]

[ "proband carried the pathogenic heteroplasmic mutation A3243 G mutation in mitochondrial 12S rRNA gene", "His brain MRI revealed abnormal signal, brain tissue swelling, and midline structure was shifted slightly to the right ( Fig. 1 A ). A large lactate peak and decreased N -acetylaspartate were found in this region on proton MRS", "Normal structure and ejection fraction were observed via echocardiography", "Serum lactate dehydrogenase, creatine kinase, α - hydroxybutyrate dehydrogenase were significantly higher than normal, whereas creatinine, sodium, and chloride were significantly lower than normal. In the cerebrospinal fluid examination, the leucocyte count was zero, red blood cell count was 210×10 6 L, chloride was slightly lower, the protein and sugar quantifications were in normal control range", "Mitochondrial sequencing revealed that the proband carried the pathogenic heteroplasmic mutation A3243 G mutation in mitochondrial 12S rRNA gene, while his parents did not carry the mutation" ]

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[ "muscle tension was identified as grade V." ]

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[ "born at 38 weeks gestation by spontaneous delivery", "had no postnatal adaptation" ]

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[ "12 - year - old", "12 - year - old" ]

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[ "mitochondrial encephalomyopathy . The proband carried the pathogenic heteroplasmic mutation A3243 G mutation in mitochondrial 12S rRNA gene .", "mitochondrial encephalomyopathy" ]

[ "Intravenous arginine", "coenzyme Q10" ]

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[ "A 20 - year - old Turner syndrome ( TS ) patient with Neurofibromatosis 1 ( NF1 ) and Tuberous sclerosis complex ( TSC ) was apparently normal till five years of age." ]

[ "developmental milestones were within normal limits", "no history of seizures", "Plexiform Neurofibroma" ]

[ "normal uterus and ovaries in pelvic ultrasound.", "Chromosome analysis of the patient confirmed with 45, XO Karyotype" ]

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[ "menarche at 12 years of age with regular menstrual cycles" ]

[ "attained menarche at 12 years of age with regular menstrual cycles", "patient studied had also shown menstruation regularly with normal breast development" ]

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[ "short stature", "cubitus valgus deformity" ]

[ "high arched palate" ]

[ "small skin lesions of the size of pin head over the face which gradually increased in size and number.", "swelling over the left forearm, about the size of a marble, which gradually increased", "Adenoma Sebaceum, Plexiform Neurofibroma Shagreen patch and Periungual Fibromas and multiple Café - au - lait spots ranging in size from 1.5 cm to 4 cm scattered all over the body", "webbing of neck, low hair line, low set ears, high arched palate" ]

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[ "20 - year - old" ]

[ "five years of age" ]

[ "Turner syndrome ( TS ) patient with Neurofibromatosis 1 ( NF1 ) and Tuberous sclerosis complex ( TSC )" ]

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[ "thrombocytopenia with a platelet count less than 10×10 9 /L" ]

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[ "A 3 - yr - old boy was admitted because of eczema, recurrent infection, and thrombocytopenia with a platelet count less than 10×10 9 /L", "was diagnosed as having WAS" ]

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[ "large deletion in the exon 1 to 11 of the WAS gene" ]

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[ "eczema," ]

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[ "3 - yr - old" ]

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[ "WAS with a large deletion in the exon 1 to 11 of the WAS gene" ]

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[ "thrombocytopenia ( 23,000/µL )", "neonatal thrombocytopenia at birth" ]

[ "diarrhea" ]

[ "Patient 1 ( UPN 1 ) is a male who was diagnosed with WAS at the age of 5 months. He presented with incidentally detected thrombocytopenia ( 23,000/µL ) with skin eczema and severe, recurrent otitis media and diarrhea on admission", "The second male patient ( UPN 2 ) presented with neonatal thrombocytopenia at birth", "Thereafter he experienced skin eczema and recurrent infections such as cellulitis and pneumonia, until he visited our hospital at 3 months old" ]

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[ "Flow cytometric analysis of peripheral blood mononuclear cells ( PBMC ) for these 2 patients revealed a defect in WASP", "the nonsense mutations, Arg211stop and Arg13stop, were confirmed by genomic analysis", "an absolute neutrophil count ( ANC ) of more than 500/µL on days 31 and 13 and a platelet count of more than 20,000/µL on days 58 and 50, for UPN 1 and UPN 2, respectively", "The elevated total eosinophil counts and serum IgE levels", "UPN 1 had a single base substitution ( C665 T ) in exon 7 that results in an amino acid change in codon 211 ( Arg211stop )" ]

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[ "respiratory distress with hypoxemia due to pulmonary edema" ]

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[ "skin eczema", "skin eczema and recurrent infections such as cellulitis", "skin rashes on the trunk in the pre - engraftment period", "Both patients were clinically well without eczematous skin" ]

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[ "5 months", "3 months old ." ]

[ "at birth" ]

[ "with" ]

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[ "XY2 is a boy of seven years of age with X - linked hypophosphatemia", "He inherited this genetic disorder from his mother, who in turn inherited it from her father", "XY2 was reported by both his parents due to a suspicion of developmental problems. The parents noticed a major head start over his peers at school level. On a social level, however, there appears to be a lag. Owing to hypophosphatemia, there has been a lack of growth.", "XY2 is the middle of the three sons in a family. Both XY1 and XY2 have been diagnosed with X - linked hypophosphatemia. Using chorionic villus sampling, the disorder has been ruled out in the youngest son, XY3. After XY2 was diagnosed as suffering from AD, the parents requested to test XY1 also. They were also concerned about his development and desired further clarity. An extensive psychiatric analysis was conducted and for XY1 an ADI - R was conducted with the parents and an ADOS - G for XY1. Both these tests gave values just below the autism threshold. His intelligence was determined using a WISC - III test. XY1 is of normal intelligence ( total IQ : 107, verbal IQ : 106, performance IQ : 107 ). In the familial anamnesis, no past history of ASD was reported. In addition, the parents, grandparents, and siblings of the parents were asked to complete a questionnaire for the calculation of autism quotient. This questionnaire has been developed to measure the degree to which an adult with normal intelligence has autistic traits. Everyone took scores ranging from below average to high average; only the paternal grandfather took a high score, which often corresponds to the score of people with autism '" ]

[ "suspicion of developmental problems. The parents noticed a major head start over his peers at school level. On a social level, however, there appears to be a lag.", "intellectually gifted ( WISC - III Full Scale IQ : 135, Verbal IQ : 136, Performance IQ : 133 )", "DSM - IV - diagnosis of AD, confirmed by the ADI - R ( autism diagnostic interview - revised ) of the parents and the ADOS - G ( autism diagnostic observation schedule )" ]

[ "molecular analysis of the PHEX gene and sequence analysis showed a hemizygote 1735 G > A(G579R ) missense mutation in exon 17 of the PHEX gene in all subjects" ]

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[ "lack of growth." ]

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[ "seven years of age" ]

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[ "X - linked hypophosphatemia" ]

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[ "the baby weighed 8.5 kg with head circumference 44 cm and length 81 cm", "Arterial oxygen saturation ( SpO 2 ) was 94 %.", "The heart rate was 146 / min. The respiratory rate was 26 / min. Non - invasive blood pressure was 73/44 ( 54 ) mm Hg." ]

[ "no history of fever, rash, abdominal pain, constipation", "Abdomen was soft. The liver was palpable 1 cm below the costal margin. The spleen was not felt. There were no other masses felt", "and liver function were within the reference range." ]

[ "Our case was a 1 - year 5 - month - old male child, brought with complaints of reddish discoloration of the nappies and clothes and breath - holding spells. There was no abnormal odor of the skin or urine. There was no history of crying while passing urine, poor urinary stream or bleeding from skin or mucus membrane. There was no history of fever, rash, abdominal pain, constipation or alteration of sensorium", "The mother of the baby was a known case of thalassemia trait; however, had never received transfusion. The baby ’s parents were consanguineous cousins. The father ’s thalassemia status could not be elicited.", "Parents ’ urine was negative for HA" ]

[ "no history of fever, rash, abdominal pain, constipation or alteration of sensorium.", "conscious and alert", "Reflexes were normal, and he had hypotonia. There was no neck stiffness. The spine and gait were normal.", "No abnormalities were detected on the electroencephalogram" ]

[ "The urine routine examination and ultrasound abdomen were normal. The hemoglobin levels were low with microcytic hypochromic anemia. Hemoglobin was 10.2 g / dl ( normal 10.5 - 14 g / dl ), packed cell volume, mean corpuscular volume ( MCV ) and mean corpuscular hemoglobin were low at 31.9 % ( normal 32 - 42 % ), 68 fl ( normal 72 - 88 fl ), and 21.8 pg ( normal 24 - 30 pg ), respectively. MCV concentration was 32 % ( normal 31.5 - 34.5 % ) and red cell distribution width 17.1 % ( normal 11 - 16 % ). Serum iron, total iron binding capacity, and ferritin levels were within the reference range. Hemoglobin analysis by cation exchange high - pressure liquid chromatography ( HPLC ) revealed Hb A0 to be 80.4 % and Hb A2 to be 6.1 % ( normal 2.40 - 3.60 ). The HPLC picture on correlation with the complete hemogram suggested β - thalassemia trait. DNA studies confirmed the beta globin gene defect of β - thalassemia. The serum electrolytes and serum bicarbonate were normal. The renal function and liver function were within the reference range. The child ’s urine porphyrin, estimations were within normal levels, and serum lead levels and δ - amino levulinic acid were not tested. Myoglobin and hemoglobin levels were undetected in urine", "Urine was of normal color when voided but turned black over variable periods spontaneously; furthermore, turned black with Benedict ’s reagent, strong alkali ( filter paper impregnated with 10 % sodium hydroxide turned black within 5 min when dipped into the urine ) and ferric chloride ( addition of dilute ferric chloride solution drop by drop showed an evanescent violet blue color ).", "Benedict ’s test was strongly positive with red brown precipitate at the bottom and black colored supernatant. Glucose oxidase test ( with multistix ) was negative excluding the role of glucose as reducing substance.", "A greenish black color developed, signifying the presence of a substantial amount of HA. Quantitative examination of urine by tandem mass spectrometry revealed that concentration of HA in urine was 91 mg / dl ( normally HA is not present in urine )" ]

[ "Examination of the cardiovascular system showed normal heart sounds. There were no added heart sounds, murmurs or rubs.", "cardiovascular systems were normal." ]

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[ "reddish discoloration of the nappies and clothes", "no abnormal odor of the skin or urine.", "no history of crying while passing urine, poor urinary stream", "Urine was of normal color when voided but turned black over variable periods spontaneously" ]

[ "breath - holding spells.", "normal chest movements with equal air entry on both sides" ]

[ "musculoskeletal system, skin, and cardiovascular systems were normal" ]

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[ "no abnormal odor of the skin", "no history of fever, rash,", "no jaundice or dehydration or abnormal odor", "skin, and cardiovascular systems were normal." ]

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[ "1 - year 5 - month - old" ]

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[ "alkaptonuric" ]

[ "low phenylalanine and tyrosine diet ," ]

[ "thrombocytopenia ( platelets 10.3 × 10 4 / μl )" ]

[ "sudden rectal hemorrhage", "no previous significant rectal bleeding.", "abdomen was soft and flat; a non - tender liver edge descended to 8.5 cm below the right costal margin, and the splenic tip was palpable 11.5 cm below the left costal margin", "extremely enlarged liver and spleen." ]

[ "A 21 - year - old male patient suffering from sudden rectal hemorrhage was admitted to a general hospital in July 2009", "no previous significant rectal bleeding.", "His past medical history was unremarkable except for occasional nasal bleeding during childhood" ]

[ "Neurologic examination revealed no evidence of abnormalities" ]

[ "thrombocytopenia and slight leukocytopenia ( platelets 6.7 × 10 4 /μl, white blood cells 3,180 / μl ). Other laboratory findings disclosed : total bilirubin 1.4 mg / dl ( reference range 0.2–1.3 ), direct bilirubin 0.5 mg / dl ( reference range 0–0.3 ), and prothrombin time activity 77.0 % ( reference range 90–130 ). To find out the cause of thrombocytopenia and leukocytopenia, we performed serology tests for infection with hepatitis B virus, hepatitis C virus, Epstein - Barr virus and Helicobacter pylori; however, there were no remarkable findings. Anti - DNA antibody test showed a titer of 1:40 ( reference range < 1:40 ). His platelet - associated immunoglobulin G ( PAIgG ) level was elevated to 166 ng/10 7 cells ( reference range 9.0–25.0 ), however anti - platelet antibody ( anti - platelet - binding IgG ) was negative. Enhanced computed tomography ( CT ) showed the extremely enlarged liver and spleen. The splenic and the superior mesenteric vein were dilated and tortuous, whereas no apparent cirrhotic change of the liver was observed ( fig. 1a ). For further examination, especially for the differential diagnosis of idiopathic portal hypertension, we performed a liver biopsy. The liver biopsy specimen showed that numerous large cells with striated cytoplasm assembled in Glisson 's capsule ( fig. 2 ). The cells had abundant eosinophilic cytoplasm with a striated or fibrillar appearance like that of crumpled tissue paper, which is typical of Gaucher cells. There was fibrous expansion of most portal tract areas, but bridging fibrosis was not seen. Additional blood investigations revealed high values of acid phosphatase and angiotensin - converting enzyme ( ACE ) concentrations ( table 1 ), which is compatible with Gaucher disease. The enzymatic activity of leukocyte β - glucosidase, the measurement of which is necessary for the definitive diagnosis of Gaucher disease, had decreased to 11.67 nmol / h / mg ( reference range 56.76–74.85 ). We analyzed the seven common mutations ( N370S, 84GG, F213I, IVS2 + 1, L444P, R463C and D409H ) in the GBA gene as previously reported with the informed consent of the patient and found the compound heterozygous mutations L444P / D409H.", "Figure 1b shows the CT scan 5 months after ERT started. The liver and the spleen were sized down ( liver : from 23.3 × 15.4 × 20.3 cm to 22.1 × 15.3 × 17.9 cm; spleen : from 12.8 × 10.5 × 21.1 cm to 11.8 × 9.4 × 17.3 cm ). Platelet counts number and ACE concentration, a biomarker of the progress of Gaucher disease, were also improved from 7.4 to 11.3 × 10 4 /μl and from 42.5 to 24.7 IU / μl, respectively ( fig. 3 ). \" }" ]

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[ "21 - year - old" ]

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[ "Gaucher disease type 1" ]

[ "enzyme replacement therapy ( ERT ) . 60 U / kg body weight imiglucerase , a macrophage - targeted recombinant human glucocerebrosidase , was injected every 2 weeks" ]

[ "length measured 50 cm ( < 5 th percentile ), weight 3000 g ( < 5 th percentile ), and head circumference 36.5 cm ( 5–10 th percentile ). She had a weak pulse, with a heart rate of about 130 beats per minute. Blood pressure was 50/40 mmHg at admission" ]

[ "cholestasis and severe intractable vomiting", "jaundice and vomiting", "recurrent vomiting, poor feeding and cholestasis", "with recurrent vomiting and poor intake which led to poor weight gain.", "Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission", "jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed" ]

[ "45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances", "A 45 days old infant with female appearing genitalia was admitted because of recurrent vomiting, poor feeding and cholestasis.", "Problems started from third day of life with recurrent vomiting and poor intake which led to poor weight gain. Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission.", "No similar presentation or family history of other features of liver or edocrine disease was reported" ]

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[ "Sepsis workups including blood culture and urine culture were performed, which later results showed both negative", "tyrosine level, laboratory assessment for metabolic disorders including serum and urine amino acid chromatography, urinary organic acid profile and NH3 and lactate levels were evaluated with all in normal range but serum alpha1 antitrypsin concentration was mildly increased. The markers for hepatitis and TORCH infections were also negative", "serum sodium 102 meq / lit and serum k + level 9 meq / lit. Total and direct bilirubin was 13.9 mg / dl and 5.4 mg / dl retrospectively. Erythrocyte sedimentation rate was 7. Thyroid function test was normal and serum glucose level by either glucose oxidas or orthotoloidas method were lower than normal but with no significant difference", "Buccal smear was negative for bar body", "Abdominal sonography showed both adrenals hypertrophic but otherwise normal. Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis", "chromosome study showed 46XY pattern", "Electrolyte abnormalities and blood sugar was corrected during first week of treatment ( Na=130 and K=4.5 Meq / lit ). One week later, the total and direct bilirubin declined to 5 and 2.5 mg / dl respectively. After one month, bilirubin levels and all of the liver function tests returned to normal" ]

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[ "electrolyte disturbances", "Hyponatremia and hyperkalemia", "with female appearing genitalia", "External genitalia seemed normal female type", "serum sodium 102 meq / lit and serum k + level 9 meq / lit.", "Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis.", "Electrolyte abnormalities and blood sugar was corrected during first week of treatment ( Na=130 and K=4.5 Meq / lit )." ]

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[ "sclerae and skin were obviously jaundiced", "Ophthalmic fundoscopy in view of corioretinitis, cataract was not conclusive" ]

[ "pallor and decreased subcutaneous fat and ill appearance with severe dehydration", "skin were obviously jaundiced" ]

[ "It was a product of consanguineous parents with birth weight of 3300 grams" ]

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[ "45 days old" ]

[ "third day of life" ]

[ "congenital adrenal hyperplasia ." ]

[ "Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting", "Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement . Electrolyte abnormalities and blood sugar was corrected during first week of treatment ( Na=130 and K=4.5 Meq / lit ) . One week later , the total and direct bilirubin declined to 5 and 2.5 mg / dl respectively . After one month , bilirubin levels and all of the liver function tests returned to normal , jaundice disappeared and acholic stools changed to normal pattern . In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed . On her most recent visit at the age of 15 months , the patient had no obvious problem ." ]

[ "pulse rate was 102 / min, blood pressure was 84/58 mm of Hg. and respiratory rate was 25 / min. Her weight was 7.9 kg, length was 70 cm and head circumference was 45 cm" ]

[ "no hepatosplenomegaly" ]

[ "An eleven month old female child, born of a primigravida mother of non - consanguinous marriage came to us with history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. Some of the blisters were at the healing stage. Mother also noticed red colored urine for last three months. Birth and developmental history were normal.", "There was no similar illness in the family" ]

[ "developmental history were normal.", "Neurological examination was normal.", "without neurological involvement", "Bright red fluorescence was also noted in the urine, teeth and blood under wood 's lamp" ]

[ "Complete blood count showed mild anemia; Hb-9.2 mg / dl, total leucocyte count-8,200 and platelet count of 1.4 lac / cumm. On peripheral smear anemia was microcytic, hypochromic in type. But, reticulocyte count was 1.2 % of circulating erythrocytes ( normal upto 2 % ). Liver and renal function tests were normal. ELISA for HIV was negative. Urinary porphobolinogen was absent. But, on screening test with a spectrophotometer urinary total porphyrin level was 1023 nmol / mmol of creatinine ( normal < 35 nmol / mmol ). Twenty four hours urinary and faecal level of uroporphyrin and coproporphyrin were also significantly elevated. The erythrocyte porphyrin level was 115.3 mcg/100 ml using the haematofluorometric method ( normal value < 40 mcg/100 ml )." ]

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[ "red colored urine for last three months.", "red colored urine", "Bright red fluorescence was also noted in the urine, teeth and blood under wood 's lamp" ]

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[ "without neurological involvement and evidence of arthritis" ]

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[ "history of recurrent blisters face and upper limbs since two months of age. Gradually blisters appeared on scalp, feet, neck and shoulders. Some of the blisters were at the healing stage", "some pallor", "Blisters were present on scalp, face, upper and lower limbs with atrophic scars on scalp and upper limbs along with alopecia", "infancy - onset blistering over sun - exposed areas, atrophic scars" ]

[ "born of a primigravida mother", "Birth and developmental history were normal." ]

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[ "eleven month old" ]

[ "since two months of age ." ]

[ "of congenital erythropoietic porphyria" ]

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[ "Spleen enlargement was also observed" ]

[ "We report on a 5 - year - old girl with a history of pink - stained urine as a newborn. Disease onset occurred in the tenth month of life. Her deciduous teeth sprouted with a red - brown color. She also suffered from episodes of burning sensation, erythema and edema on her face, neck, arms and lower legs within minutes following exposure to direct sunlight in her infancy. Vesicles or subepidermal bullous lesions progressed to crusted erosions, which healed with scarring and either hyperpigmentation or hypopigmentation ( fig. 1a ). They appeared constantly and got worse during the spring and summer months. Hypertrichosis developed on unprotected skin areas.", "Her brother had died of a disease similar to hers in terms of symptoms and abnormalities, suggesting that he had the same gene mutation ( V3F ). Conversely, on the basis of the pedigree analysis spanning three generations, no other symptomatic patients were found" ]

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[ "Urine porphyrins were extremely elevated to 16 μmol / dl with a predominance of coproporphyrins and uroporphyrins", "accumulation of porphyrins in the blood", "A single missense mutation corresponding to a G - to - T transversion ( 11,776 g > t ) in exon 2 was found, leading to an amino acid change from valine at position 3 to phenylalanine ( fig. 2 ). The result indicated that the patient was homozygous for this mutation. Then, we also analyzed the UROS genes of her parents who were shown to be heterozygote carriers of this mutation", "The specific activity of the mutated UROS was less than 16.1 % that of the control." ]

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[ "pink - stained urine as a newborn", "history of pink - stained diapers" ]

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[ "episodes of burning sensation, erythema and edema on her face, neck, arms and lower legs within minutes following exposure to direct sunlight in her infancy. Vesicles or subepidermal bullous lesions progressed to crusted erosions, which healed with scarring and either hyperpigmentation or hypopigmentation ( fig. 1a ). They appeared constantly and got worse during the spring and summer months. Hypertrichosis developed on unprotected skin areas.", "Severe cutaneous photosensitivity, blistering of light - exposed skin", "bullae healed, leaving milia and hyperpigmented scars" ]

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[ "5 - year - old" ]

[ "Disease onset occurred in the tenth month of life" ]

[ "CEP" ]

[ "strict avoidance of UV and visible light , use of topical sunscreen ," ]

[ "anemia" ]

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[ "A 20 - year - old unmarried, young girl from the remote village of South Bengal, who had slightly poor physical but normal mental development, presented with occasional high rise of temperature, frequent dental caries, and fall - out of teeth from time to time since the age of 3–4 years along with persistent thickening, flaking, and scaling of the skin of her palms and soles for past 14 years. She also complained of poor formation of saliva ( xerostomia ), poor formation of tear ( xerophthalmia ), recurrent conjunctivitis, alopecia, frequent pharyngitis, otitis, rhinitis, and pyogenic skin lesions since childhood.", "The past dental history revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years. Similarly, her permanent teeth too were lost prematurely after having erupted normally. At the age of 6 years, her parents had noticed the presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands by the age of 9–10 years. The remainder of her past medical history was unremarkable.", "There was a family history of acquired palmoplantar keratodermas of her parents. She also informed that many of her neighbors of her locality had similar palmar - plantar hyperkeratosis without any other complaints she presented, particularly dental problems.", "similar palmo - plantar hyperkeratotic lesions of her parents and of few neighbors" ]

[ "normal mental development," ]

[ "Routine hematological examinations and routine biochemical examinations revealed normal results, except for anemia", "Serological tests like anti - nuclear antibody, anti - cytoplasmic neutrophilic antibody, HIV - I and II, and VDRL were negative", "Chest X - ray posterior - anterior view was within normal limit. Orthopantomonograph ( OPG ) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “ floating in air ” appearance.", "Neutron activation analysis of hair and nail proved the diagnosis of chronic arsenicosis" ]

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[ "frequent dental caries,", "fall - out of teeth from time to time", "poor formation of saliva ( xerostomia ), poor formation of tear ( xerophthalmia ), recurrent conjunctivitis,", "frequent pharyngitis, otitis, rhinitis,", "her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4–6 years.", "permanent teeth too were lost prematurely after having erupted normally", "patient′s central incisors, mandibular lateral incisors, maxillary first premolars, and all permanent first molars were missing. All permanent teeth that were present exhibited marked mobility and were malformed, rudimentary, and conical or pegged teeth. Enamel defects were present with dental caries.", "Orthopantomonograph ( OPG ) of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots, giving the teeth a “ floating in air ” appearance." ]

[ "persistent thickening, flaking, and scaling of the skin of her palms and soles", "alopecia", "pyogenic skin lesions", "presence of rough skin on the plantar surface of her feet, with subsequent involvement of the palmar surface of the hands", "there were symmetrical, well - demarcated, keratotic, and confluent plaques affecting the skin of the palms and soles. The skin was dry and rough on palpation. She also had chronic eczematous dermatitis in elbows and knees, few areas of hypo / hyper - pigmentation of anterior and posterior part of the chest. Her hair was sparse, fine, and lusterless, brittle along with alopecia; she also had decreased body hair and sparse or absent eyebrows and eyelashes", "mild to moderate pallor", "palmo - planter hyperkeratosis." ]

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[ "20 - year - old" ]

[ "since the age of 3–4 years" ]

[ "chronic arsenicosis" ]

[ "standard dose of penicillamine as a chelating agent" ]

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[ "upper abdominal discomfort for 15–20 days", "pendulous abdomen.", "hepatomegaly", "protuberant abdomen" ]

[ "A 12 - year - old boy was brought to the hospital by his parents with upper abdominal discomfort for 15–20 days" ]

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[ "USG study of the abdomen showed hepatomegaly with diffusely raised echogenicity and a 7.5 × 4.5 cm – sized, well - defined, hypoechoic mass lesion in segment VI of the right lobe of the liver. CT scan of the abdomen showed hepatomegaly with diffuse low attenuation of the liver and a 7.5 × 4.5 × 4.8 cm well - circumscribed, low - attenuation, subcapsular focal lesion in segment VI of the right lobe; this lesion showed mild to moderate heterogeneous contrast enhancement and had a nonenhancing area within it. Multiple small bilateral renal calculi were also noted.", "increased uric acid levels and raised cholesterol. The random blood sugar level was 60 mg%. Liver function tests were within normal limits", "histopathological examination along with a small bit of liver tissue, which showed PAS - positive glycogen - rich hepatic cells, confirming glycogen deposition in the liver, while the lesion itself was confirmed to be a hepatic adenoma." ]

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[ "Multiple small bilateral renal calculi were also noted.", "bilateral renal calculi" ]

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[ "retarded growth ( dwarfism )", "clinical features of dwarfism" ]

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[ "facial dysmorphism" ]

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[ "12 - year - old" ]

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[ "An 18 - month - old boy born after an uncomplicated full - term pregnancy was hospitalized for psychomotor regression and drug - resistant myoclonic epilepsy.", "There was a consanguinity of the first degree of the parents and the death of a brother at the age of 16 months under unspecified circumstances. The other brother and sister were unaffected.", "The onset of clinical symptoms began at the age of 6 months with myoclonus of the face and upper limbs, recurrent fever and psychomotor developmental delay." ]

[ "psychomotor regression and drug - resistant myoclonic epilepsy.", "myoclonus of the face and upper limbs,", "psychomotor developmental delay.", "macrocephaly of 51 cm", "axial hypotonia with no further optical problems or responsiveness to light", "Cerebral computed tomography ( CT ) scanning performed without contrast medium injection showed a bilateral thalamic hyperdensity with hypodensity of the white matter ( Fig. 1 ).", "With magnetic resonance imaging ( MRI ) the thalamus was hyperintense on T1 - weighted images and hypointense on T2 - weighted images ( Fig. 2 ) with an increased T2 signal of the white matter. No imaging changes could be observed in the caudate nucleus, putamen, globus pallidum and brainstem" ]

[ "Cerebral computed tomography ( CT ) scanning performed without contrast medium injection showed a bilateral thalamic hyperdensity with hypodensity of the white matter ( Fig. 1 ). With magnetic resonance imaging ( MRI ) the thalamus was hyperintense on T1 - weighted images and hypointense on T2 - weighted images ( Fig. 2 ) with an increased T2 signal of the white matter. No imaging changes could be observed in the caudate nucleus, putamen, globus pallidum and brainstem" ]

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[ "no further optical problems or responsiveness to light.", "cherry - red spot without optic atrophy" ]

[ "dysmorphic syndrome consisting of a frontal bossing and a broadening of the nasal bridge" ]

[ "born after an uncomplicated full - term pregnancy" ]

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[ "18 - month - old" ]

[ "The onset of clinical symptoms began at the age of 6 months" ]

[ "Sandhoff disease" ]

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[ "blood pressure and other vital signs were normal" ]

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[ "A 21 - year - old nullipara presented with asymptomatic pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture, and was not preceded by trauma or any general symptom such as fever", "The patient had been married for 2 years. She had no history of abortion or any systemic complaints", "Her family history was not contributory" ]

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[ "The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X - ray and EKG were also normal", "The feces was negative for occult blood", "Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid - dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium" ]

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[ "mucosa over the hard palate showed small, firm, yellowish - white plaques", "Ocular examination did not reveal any abnormality" ]

[ "pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture,", "multiple brownish - black papules symmetrically distributed over the front and sides of the neck and periumbilical area. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal", "fragmented, irregularly clumped, basophilic material throughout the mid - dermis. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium." ]

[ "nullipara", "no history of abortion" ]

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[ "21 - year - old" ]

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[ "PXE" ]

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[ "vital signs were a blood pressure of 115/92 mmHg, a regular pulse of 105 / min, and a respiratory rate of 18 / min. His height was 152.5 cm ( < 3th percentile ) and body weight was 72.5 kg. The body mass index was 32.5." ]

[ "dark urine, and jaundice" ]

[ "A 41 - yr - old man was referred to our emergency room from a local clinic on July 3, 2006, with the impression of acute viral hepatitis due to a remarkable elevation of liver enzymes. He had experienced generalized weakness, dark urine, and jaundice for a two week period. His previous history included community - acquired pneumonia and carpal tunnel syndrome, but neither diabetes mellitus nor hypertension. He complained of impotence, and his mother described precocious puberty and hirsutism beginning at the age of 7. He was not married and had no children." ]

[ "generalized weakness,", "carpal tunnel syndrome," ]

[ "Total and direct bilirubin levels were elevated at 11.6 mg / dL and 8.6 mg / dL, respectively. The AST and ALT levels were 224 and 1,044 U / L, respectively. Serum BUN level was 9.7 mg / dL, and serum creatinine level was 0.82 mg / dL. Serum electrolytes were normal. Based on a positive anti - HAV IgM titer, he was diagnosed with acute hepatitis A. During the evaluation to exclude other causes of liver dysfunction, a 4 × 2.3 cm left adrenal mass and bilateral adrenal hyperplasia were incidentally noted on abdominal CT ( Fig. 2A, B ). We evaluated the endocrine function ( Table 1 ). Twenty - four hour urine catecholamines and VMA were within the normal range. However, hypercortisoluria was noted in 2 independent measurements ( 226.4 µg/24 hr; 122.1 µg/24 hr ). Plasma cortisol was within the normal range ( 7.4 µg / dL ), however, ACTH level was very high ( 676.5 pg / mL ). Urine 17 - OHCS and 17 - ketosteroid levels were markedly elevated to 123.0 mg/24 hr and 54.6 mg/24 hr, respectively. Serum aldosterone level was marginally elevated ( 0.414 ng / mL ). DHEA - S was within the normal range ( 1.88 µg / mL ). Based on the high serum ACTH level, hypercortisoluria, and bilateral adrenal hyperplasia with a large left adrenal mass", "The testosterone level was normal ( 3.51 ng / mL ), but 17α - hydroxyprogesterone ( 17 - OHP ) was markedly elevated to 30,000 ng / dL, strongly supporting the diagnosis of a simple virilizing form of CAH", "compound heterozygote for CYP21 mutations : Ile173Asn ( I173N ) and Arg357Trp ( R357W ) ( Fig. 3 ), confirming the diagnosis of a simple virilizing from of CAH due to mutations in CYP21" ]

[ "nor hypertension" ]

[ "neither diabetes mellitus", "precocious puberty", "Acanthosis nigricans was present in both axillae,", "central obesity", "rather ambiguous buffalo hump; however, moon face or red stria was not present", "4 × 2.3 cm left adrenal mass and bilateral adrenal hyperplasia were incidentally noted on abdominal CT", "Twenty - four hour urine catecholamines and VMA were within the normal range. However, hypercortisoluria was noted in 2 independent measurements ( 226.4 µg/24 hr; 122.1 µg/24 hr ). Plasma cortisol was within the normal range ( 7.4 µg / dL ), however, ACTH level was very high ( 676.5 pg / mL ). Urine 17 - OHCS and 17 - ketosteroid levels were markedly elevated to 123.0 mg/24 hr and 54.6 mg/24 hr, respectively. Serum aldosterone level was marginally elevated ( 0.414 ng / mL ). DHEA - S was within the normal range ( 1.88 µg / mL ).", "high serum ACTH level, hypercortisoluria, and bilateral adrenal hyperplasia with a large left adrenal mass", "24 - hr urine cortisol was markedly suppressed, not only by high - dose dexamethasone but also by low - dose dexamethasone", "short stature, precocious pubarche and marked suppression of 24 - hr urine cortisol by dexamethasone suggesting hyperresponsiveness of the adrenal cortex to ACTH", "The testosterone level was normal ( 3.51 ng / mL ), but 17α - hydroxyprogesterone ( 17 - OHP ) was markedly elevated to 30,000 ng / dL,", "After 6 months of treatment with dexamethasone ( 0.25 mg daily ), bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size", "17 - OHP and ACTH levels were normalized to 118 ng / dL and 20.8 pg / mL" ]

[ "dark urine", "impotence,", "Serum BUN level was 9.7 mg / dL, and serum creatinine level was 0.82 mg / dL. Serum electrolytes were normal.", "impotence was improved" ]

[ "community - acquired pneumonia" ]

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[]

[ "hirsutism", "Acanthosis nigricans was present in both axillae", "erythematous, scaly, guttate papules on the lower abdominal skin", "rather ambiguous buffalo hump; however, moon face or red stria was not present" ]

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[]

[ "41 - yr - old" ]

[ "age of 7" ]

[ "Gene analysis revealed CAH due to 21 - hydroxylase deficiency" ]

[ "administration of adrenal steroids . After 6 months of treatment with dexamethasone ( 0.25 mg daily ) , bilateral adrenal hyperplasia and tumorous growth in left adrenal gland were substantially decreased in size ( Fig . 2C , D ) . 17 - OHP and ACTH levels were normalized to 118 ng / dL and 20.8 pg / mL , respectively , and impotence was improved ." ]

[ "normal complete hemogram ( including hemoglobin, total leukocyte count, differential leukocyte count )," ]

[ "recurrent episodes of diarrhea" ]

[ "The second case was of a 28 - year - old male who was born of a non - consanguineous marriage, had delayed psychomotor milestones with mental retardation, congenital cataract, and recurrent episodes of diarrhea since early childhood. He had history of progressive spastic diplegia, tremulousness in both upper limbs and scanning speech. The patient had impaired attention, vigilance, comprehension, and new learning ability.", "A 50 - year - old commerce graduate with degree in law presented to us with insidious onset gradually progressive spastic diplegia for 20 years followed later by gradually progressive bladder dysfunction, poor scholastic performance, and a single seizure. He was born to non - consanguineous parents and had unremarkable early psychomotor development. Pedigree analysis revealed absence of any family history in previous two generations." ]

[ "delayed psychomotor milestones with mental retardation", "progressive spastic diplegia, tremulousness in both upper limbs and scanning speech.", "impaired attention, vigilance, comprehension, and new learning ability.", "Pan - sensory impairment was noted below knee with impaired limb coordination in upper limbs", "MRI brain showed altered signals in bilateral cerebral peduncles, ventral pons, both the middle cerebellar peduncles and medullary pyramids", "progressive spastic diplegia for 20 years", "gradually progressive bladder dysfunction, poor scholastic performance, and a single seizure.", "unremarkable early psychomotor development.", "impairment of attention, new learning and visual memory with normal language functions. His speech was slow and slurred but could be comprehended with little difficulty. All cranial nerve functions were intact. The patient had severe spasticity in both lower limbs with brisk deep tendon reflexes in both the upper and the lower limbs, extensor plantar responses, and normal sensory examination", "MRI brain showed T2 - weighted hyperintensities in dentate nucleus regions bilaterally and generalized cerebral and cerebellar atrophy" ]

[ "Patient 's skin biopsy of swelling over Achilles confirmed xanthoma", "MRI brain showed altered signals in bilateral cerebral peduncles, ventral pons, both the middle cerebellar peduncles and medullary pyramids", "Blood investigations revealed a normal complete hemogram ( including hemoglobin, total leukocyte count, differential leukocyte count ), liver and kidney function tests, serum electrolytes and, triglyceride and cholesterol levels.", "X - rays of ankle, knee, and elbow showed homogenous soft tissue swelling. MRI brain showed T2 - weighted hyperintensities in dentate nucleus regions bilaterally and generalized cerebral and cerebellar atrophy", "Plasma cholestanol levels were found to be raised suggesting cerebrotendinous xanthomatosis", "The analysis revealed heterozygous mutation in exon 6 with substitution of cytosine by thymine at 1151 position ( c. 1151C > Tp. P384L ) and a novel mutation in exon 1 of CYP 27 gene with substitution of thymine by cytosine at nucleotide position 2 of the gene ( c. 2 T > Cp. M1 T )" ]

[]

[]

[ "gradually progressive bladder dysfunction" ]

[]

[ "thoracic kyphosis with contractures at hip, knee, and ankle joints" ]

[ "congenital cataract," ]

[ "skin biopsy of swelling over Achilles confirmed xanthoma.", "firm, non - tender swellings over ankles, patella, and elbows bilaterally", "homogenous soft tissue swelling." ]

[]

[]

[ "28 - year - old", "50 - year - old" ]

[ "since early childhood" ]

[ "CTX" ]

[ "atorvastatin besides physical therapy and chenodeoxycholic acid ( CDCA ) is being arranged" ]

[]

[]

[ "A 5 year - old boy was referred to the Pediatric Dentistry Clinic with the complaint of \" a small ball that appeared in the mouth \"", "The child was the third twin; however, the parents as well as the siblings, did not have the metabolic disorder" ]

[]

[ "Radiographic examinations included periapical, panoramic and occlusal views showing pulp chambers enlarged, with pulp horns extending to the dentino - enamel junction, poorly defined lamina dura and hypoplastic alveolar ridge" ]

[]

[ "hypophosphatemic vitamin D - resistant rickets" ]

[]

[]

[ "short stature and several skeletal abnormalities" ]

[ "small ball that appeared in the mouth", "fistula at the periapical region of primary maxillary left lateral incisor without caries or trauma", "complete primary dentition and none of the teeth examined showed evidence of caries" ]

[]

[]

[]

[ "5 year - old" ]

[]

[ "hypophosphatemic vitamin D - resistant rickets" ]

[ "calcitriol and phosphate supplements" ]

[ "gingival bleeding during brushing and eating, after the eruption of permanent teeth", "gingiva, with excessive bleeding", "bleeding on probing with deep periodontal pockets." ]

[]

[ "The family history revealed consanguineous marriage of the parents. The parents and other family members were not affected", "Medical history was non - contributory", "Natal history revealed that the patients presented with eruptions on the scalp, legs, feet, arms, and hands at birth, for which the parents did not seek any treatment. Subsequently, there was reddening of the palms and soles at 6 months of age, which gradually thickened and became rough and scaly. These symptoms were worse during the winter season", "Case 2 ' : ' An 11 - year - old girl, younger sibling, had mixed dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth with halitosis were present.", "A 16 - year - old boy ( case 1 ) presented to the Department of Dentistry, DR. R. P. Government Medical College, Kangra at Tanda, Himachal Pradesh with the chief complaint of loose teeth and markedly inflamed gingiva, with excessive bleeding and severe halitosis", "The patient had one younger female sibling, 11 - year - old girl ( case 2 ) who also showed trait of PLS. \"", "' A 16 - year - old boy had permanent dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth, with heavy deposits of plaque and calculus and halitosis were also present." ]

[ "steady gait", "mental development was also normal" ]

[ "The radiographic examination using panoramic and periapical films showed severe alveolar bone loss up to the apical third region of the roots of the permanent teeth that were present, giving them the characteristic “ floating - teeth ” appearance. On lateral cephalogram, there was no evidence of intracranial calcification in both patients", "Laboratory investigation was carried out, which included hematological and biochemical assessment. Routine blood investigations and liver function tests were found to be within the normative range of values", "The radiographic examination using panoramic film showed extensive bone loss and areas suggestive of vertical defects. ' }" ]

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[ "resorption of the alveolar ridge", "deciduous teeth had erupted normally, but there had been early shedding, starting at age of 3 years and complete shedding of all deciduous teeth by the age of 6 years. The mother reported that all of the patient 's primary teeth were prematurely lost due to hypermobility. There had been normal eruption of all permanent teeth, but gradually the teeth had started becoming mobile and this was followed by exfoliation of the teeth and also described gingival bleeding during brushing and eating, after the eruption of permanent teeth.", "mixed dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth with halitosis were present", "severe alveolar bone loss up to the apical third region of the roots of the permanent teeth that were present, giving them the characteristic “ floating - teeth ” appearance", "loose teeth and markedly inflamed gingiva, with excessive bleeding and severe halitosis.", "permanent dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth, with heavy deposits of plaque and calculus and halitosis were also present. The patient was found to be completely edentulous in the mandibular right quadrant. In the other quadrants, the permanent teeth that were missing were the right maxillary first molar, the right maxillary first premolar and second premolar, the lateral incisors, the central incisors, the left maxillary second premolar. All the permanent teeth that were present exhibited marked mobility. The gingiva adjacent to the teeth appeared red, inflamed and edematous. There was bleeding on probing with deep periodontal pockets. Gingival recession was present in all the teeth. The mucosa of the edentulous area appeared normal." ]

[ "eruptions on the scalp, legs, feet, arms, and hands at birth", "reddening of the palms and soles at 6 months of age, which gradually thickened and became rough and scaly. These symptoms were worse during the winter season", "increased keratinization of the skin of the palmar and plantar surfaces as well as the skin over the dorsal surfaces of the joints of the hands; the keratinized skin was clearly demarcated from adjacent normal skin. Deep fissures were present on the soles of feet. His nails and hair were normal", "Patient had a reduced facial height due to resorption of the alveolar ridge" ]

[ "Mother had a full term normal uneventful pregnancy.", "Natal history revealed that the patients presented with eruptions on the scalp, legs, feet, arms, and hands at birth," ]

[]

[ "11 - year - old", "16 - year - old", "16 - year - old" ]

[ "at birth", "1 st year of life" ]

[ "PLS" ]

[]

[ "height : 145 cm, weight : 46 Kg, body mass index ( BMI ): 21.8, Tanner staging : 1" ]

[]

[ "family 's concern about her ambiguous genitalia", "surgery ( vaginoplasty ) when she was 3 years old", "she had been admitted in hospital 2 times because of electrolytes imbalance", "The case is a 14 - year old girl with male phenotype who is a known case of congenital adrenal hyperplasia" ]

[ "good strength and excessive fatigue after exercise" ]

[ "karyotype was XX" ]

[]

[ "girl with male phenotype", "voice deepening and short stature", "Tanner staging : 1 ( Fig. 1 ), lack of menstrual period, clitoral enlargement", "ambiguous genitalia", "admitted in hospital 2 times because of electrolytes imbalance", "excessive fatigue and vomiting due to electrolytes imbalance" ]

[ "girl with male phenotype", ", lack of menstrual period, clitoral enlargement,", "ambiguous genitalia," ]

[]

[ "increased muscle bulk", "short stature.", "prolonged dysfunction due to her ankle sprain" ]

[]

[ "hirsutism", "dark skin" ]

[]

[]

[ "14 - year old" ]

[]

[ "Congenital Adrenal Hyperplasia ( C.A.H ) due to 21 hydroxylase deficiency" ]

[ "In her drug history , she had been using 30 mg hydrocortisone daily in three divided doses ( 15.8 mg / m 2 · d ) plus 100 mg fludrocortisone daily in 2 divided doses , but recently her drug doses had been changed to 7/5 mg prednisolone in the morning and 5 mg at night" ]

[ "mild thrombocytopenia, a bone marrow ( BM ) examination was performed at the age of 51, disclosing the presence of foamy macrophages classified as Gaucher cells ( GCs )", "thrombocytopenia" ]

[ "diarrhea, poor appetite" ]

[ "consultation concerning suspected Gaucher disease", "partial resection of the right lung due to an aspergilloma" ]

[ "mild tremor" ]

[ "mutations of c.1226A > G ( N370S ) and RecNci I ( L444P, A456P, and V460V ) in the GBA1 gene", "recurrent positivity for M. avium and A. fumigatus was detected", "bone marrow ( BM ) examination was performed at the age of 51, disclosing the presence of foamy macrophages classified as Gaucher cells ( GCs ).", "Radiological examination disclosed mild pulmonary fibrosis and aspergillosis in the right lung. The microbiological examination of secretions from a bronchoalveolar lavage ( BAL ) showed growth of Aspergillus fumigatus and mycobacteria other than tuberculosis ( MOTT )", "Echocardiography showed septal left ventricular hypertrophy, normal systolic function of the left ventricle ( EF of 50%–60 % ), signs of diastolic dysfunction, mild insufficiency of both aortic and pulmonary valves, and a slightly elevated pressure in the pulmonary artery ( PA ) of 42 mmHg.", "Repeated microbiological examination of the BAL secretions revealed a growth of Aspergillus fumigatus and Aspergillus nidulans, but was negative for MOTT. HIV serology was negative, excluding acquired immunodeficiency syndrome ( AIDS ).", "Chest X - ray did not show any active pathological lesions. However, computed tomography imaging ( CT ) revealed pronounced fibrosis of lung parenchyma", "absence of glucocerebrosidase activity in peripheral blood leukocytes and an increased activity of plasma chitotriosidase", "direct DNA sequencing of the GBA1 gene revealed heterozygous mutations in the GBA1 gene", "CT of the chest disclosed a new infiltrate in the lower lobe of the right lung", "recurrently positive for Mycobacterium avium in his sputum,", "positive for Aspergillus fumigatus in sputum." ]

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[]

[ "recurrent pulmonary aspergillosis caused by Aspergillus fumigatus", "chronic cough", "mild pulmonary fibrosis and aspergillosis in the right lung", "microbiological examination of secretions from a bronchoalveolar lavage ( BAL ) showed growth of Aspergillus fumigatus and mycobacteria other than tuberculosis ( MOTT )", "pulmonary bleeding", "shortness of breath and cough.", "Repeated microbiological examination of the BAL secretions revealed a growth of Aspergillus fumigatus and Aspergillus nidulans, but was negative for MOTT.", "control spirometry showed only moderately decreased results ( VC 3.72 L, 82 %; FEV 1 3.04 L, 84 %; FEV 1 /SVC 82 %; FVC 3.72 L, 82 % ).", "Chest X - ray did not show any active pathological lesions. However, computed tomography imaging ( CT ) revealed pronounced fibrosis of lung parenchyma", "increased susceptibility to pulmonary infections,", "lung involvement", "cough, and a microbiological examination of the BAL secretions revealed growth of Aspergillus fumigatus ( sensitive to voriconazole ) and Mycobacterium avium", "pulmonary infections", "after 10 days his cough decreased but, after some days, returned,", "CT of the chest disclosed a new infiltrate in the lower lobe of the right lung", "cough and night sweats were clearly reduced", "recurrently positive for Mycobacterium avium in his sputum", "positive for Aspergillus fumigatus in sputum." ]

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[]

[ "65 - year - old" ]

[]

[ "GD1", "Gaucher disease" ]

[ "miglustat , which was considered the first line of GD1 treatment at that time due to the worldwide supply shortage of Cerezyme ® during 2009–2010 ( 9 ) . He received the commercially available miglustat capsules at a dose of 100 mg three times a day orally .", "After the Cerezyme ® supply shortage had ceased , the patient was offered to start ERT" ]

[ "As a 3 - week - old neonate, she received a blood transfusion for, it was believed, hemolytic anemia of the newborn. In all three of her hospital admissions, a mild hemolytic anemia was diagnosed", "moderate hemolytic anemia was also found ( red blood cells : 3.68 × 10 6, hemoglobin : 10.6 g / dl, hematocrit : 33.0 %, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G / DL, platelets 124 × 10 3 ml, white blood cells : 3.6 × 10 3, reticulocytes : 58 ( 5 - 15 ) ), but did not require a blood transfusion" ]

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[ "At the age of 6 months, the patient was referred to our hospital for investigation of episodes of red urine.", "hemolytic anemia of the newborn", "At the age of 6 years, she was again admitted for investigation, on this occasion with a main complaint of easy skin blistering and scarring. It was noted that the intensity of the red coloration of the urine varied from day to day" ]

[ "intellectual development was normal" ]

[ "moderate hemolytic anemia was also found ( red blood cells : 3.68 × 10 6, hemoglobin : 10.6 g / dl, hematocrit : 33.0 %, MCV 89.7, MCH 28.8 pg, MCHC 32.1 G / DL, platelets 124 × 10 3 ml, white blood cells : 3.6 × 10 3, reticulocytes : 58 ( 5 - 15 ) ),", "urea, creatinine, uric acid, electrolytes, and alkaline phosphatase were normal.", "Ultrasound examination of the kidneys and heart were normal and bone densitometry was unremarkable.", "Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. High - pressure liquid chromatography of the urine demonstrated 85 % of the uroporphyrin to be of isomer I type and fecal fractionation showed mainly coproporphyrin isomer I. Urinary aminolevulinic acid and porphobilinogen levels were within normal limits. The erythrocyte protoporphyrin level was greatly increased in both zinc and free forms. Plasma fluorescence spectroscopy revealed a prominent emission peak at 617", "Molecular genetic analysis of the UROS gene revealed the sequence variant c.217T > C ( p. Cys73Arg ) in exon 4 and c.683c > T ( p. Thr228Met ) in exon 10" ]

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[]

[ "episodes of red urine.", "intensity of the red coloration of the urine varied from day to day.", "Ultrasound examination of the kidneys and heart were normal" ]

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[]

[ "lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust", "teeth have progressively stained brownish - red" ]

[ "easy skin blistering and scarring", "multiple blistering and scarring on areas of the skin exposed to the sun and hypertrichosis on the back", "severe photosensitive skin damage that had started in early childhood has led to disfiguring deformity of the face and hands.", "scarring of her skin at sun - exposed sites, including the backs of the hands, her face, and ears, and has resulted in bald patches on the scalp", "restricted hand function due to scarring of the skin and has lost some of her eyelashes, which has made her eyes prone to irritation from small particles of dust", "Moderate hypertrichosis on the back of the neck was also noted" ]

[ "born at term after an uneventful pregnancy and delivery. Her birth weight and length were 2 900 g and 51 cm, respectively" ]

[]

[ "14 years" ]

[ "3 - week - old" ]

[ "These results confirmed a diagnosis of CEP" ]

[ "6 months ," ]

[ "His vital signs were stable, with a blood pressure of 150/80 mmHg, pulse rate of 84 / min, respiratory rate of 24 / min, and body temperature of 36 ℃." ]

[ "become nauseated, and vomited", "nauseated, and developed severe vomiting.", "recurrent abdominal pain", "no evidence of gastrointestinal bleeding", "no evidence of chronic liver disease" ]

[ "A 59 - yr - old man was admitted to our hospital because he had exhibited progressive lethargy and confusion since the early morning. He had often complained of fatigue over the previous 3 months. Three days prior to presentation, he had eaten a large amount of dog meat at a party, become nauseated, and vomited. The next day, he had eaten chicken and freshwater snails, had again become nauseated, and developed severe vomiting. On the day of admission, he failed to arise at his normal time and exhibited inappropriate behavior and drowsiness. During his childhood, the patient had suffered recurrent abdominal pain and periodic episodes of convulsions, but he had not experienced any seizures in adulthood." ]

[ "progressive lethargy and confusion since the early morning.", "fatigue over the previous 3 months.", "failed to arise at his normal time and exhibited inappropriate behavior and drowsiness.", "periodic episodes of convulsions", "not experienced any seizures in adulthood", "was in a semi - coma; his Glasgow Coma Scale score was 10/15, and he was disoriented in time, place, and person", "computed tomography ( CT ) and diffusion - weighted magnetic resonance imaging revealed no brain lesions", "The cerebrospinal fluid was normal upon examination", "remained confused", "generalized tonic - clonic seizure", "seizure subsided, but the patient continued to move convulsively", "nonconvulsive status epilepticus", "patient was still semi - comatose,", "electroencephalogram did not show any signs of epileptic discharge", "mental status returned to normal" ]

[ "Laboratory investigations showed that he had hyperammonemia ( 143.8 mM ), elevated liver enzymes ( alanine aminotransferase, 179 U / L; aspartate aminotransferase, 91 U / L ), a total bilirubin level of 1.91 mg / dL, and a blood glucose level of 106 mg / dL. His blood urea nitrogen and serum creatinine levels were 17.7 mg / dL and 1.01 mg / dL, respectively. Blood analysis revealed mild leukocytosis ( 10.41 × 10 3 leukocytes/µL ) and a normal hemoglobin level, platelet count, and clotting profile. Serum electrolyte analysis showed mild hypernatremia ( 149 mEq sodium / L ), but serum potassium and chloride levels were within normal range. Results of a toxicology screen were normal.", "Further investigations revealed no evidence of gastrointestinal bleeding, and computed tomography ( CT ) and diffusion - weighted magnetic resonance imaging revealed no brain lesions. Abdominal CT imaging did not show any abnormality. The cerebrospinal fluid was normal upon examination.", "serum ammonia level increased to 370 mM", "serum ammonia level had decreased to 170 mM, but it soon rose to 228 mM. Plasma and urine amino acid analysis and urine organic acid quantitation were performed", "serum ammonia level had decreased to 36 mM. However, because it rose to 107 mM by the afternoon", "serum ammonia level stabilized at less than 30 mM. A plasma amino acids analysis revealed elevated ornithine ( 196 µM; normal 19 - 81 µM ), decreased citrulline ( 3 µM; normal 19 - 62 µM ), and elevated glutamine and lysine. Urine organic acids analysis revealed highly elevated urinary orotic acid ( 603.5 mg / mg creatinine ) and a mild urinary uracil peak" ]

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[ "59 - yr - old" ]

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[ "late - onset ornithine carbamoyltransferase deficiency" ]

[ "arginine ( 3 g ) and sodium benzoate ( 3 g ) were administered via nasogastric tube every 4 - 6 hr . Dextrose solution ( 10 % ) was supplied intravenously , and a protein - free formula was supplied via a feeding tube", "He continued to receive sodium benzoate ( 3 g ) and arginine ( 3 g ) three times daily . The protein - free formula , which was administered continuously , was gradually changed to increase the dietary protein without a significant rise in serum ammonia levels" ]

[ "Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits", "bleeding gums." ]

[]

[ "An 18 - year - old boy reported to the department of Periodontology and Implant Dentistry, Bharati Vidyapeeth University Dental College and Hospital, Navi - Mumbai for the treatment of generalized mobility of teeth and bleeding gums. Family history was important and contributory. There was a history of consanguineous marriage of the parents. Both parents were healthy. History reveled that his 16 - year - old brother also complained of similar problems. Systemic history - both the cases showed marked palmoplantar hyperkeratosis. Both patients were alert and cooperative. Onset of skin disorder was by the age of 2 - 3 years. Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows." ]

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[ "Orthopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds", "Complete blood count, serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits", "Orthopantomograph showed severe horizontal bone loss.." ]

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[ "more teeth present", "generalized mobility of teeth and bleeding gums.", "patient had lost most of his permanent teeth and the remaining teeth showed grade II mobility." ]

[ "considerable hyperkeratosis of palms and soles", "marked palmoplantar hyperkeratosis", "Scaly skin lesions began to appear by third year of age, later fissures appeared on palms and soles. Intense itching was noted and skin lesions went on to involve fingers, knees and elbows.", "bilateral hyperkeratosis of palms, soles, dorsal surface of fingers and knees" ]

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[ "18 - year - old" ]

[ "age of 2 - 3 years ." ]

[ "Papillon - Lefevre syndrome" ]

[]

[ "height of 158 cm ( – 1 SD ), weight of 85 kg ( > 2 SD ), body mass index ( BMI ) of 34.13 kg / m 2 ( greater than the 97th centile ) and blood pressure of 150/80 mmHg." ]

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[ "A 15 - yr - old male patient was referred to our department with a one - year history of gradual worsening of tremors.", "healthy, second - degree consanguineous parents", "He was diagnosed, at 40 d old, with salt - wasting 21 - hydroxylase deficiency CAH based on acute dehydration, salt loss syndrome", "hypertension at 8 yr of age", "Two adrenal crises occurred at one and nine years of age and were precipitated by viral illnesses" ]

[ "Neurological examination objectified postural and action tremor in upper limbs with static kinetic cerebellar syndrome more pronounced on the left, tetra pyramidal reflex syndrome and moderate mental decline", "Brain MRI showed bilateral periventricular white matter hyperintensity on T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2 - weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity ( arrow ) and cortico - subcortical atrophy. Fig. 2 FLAIR - weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity ( arrow ) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1 - weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico - subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 ).", "Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected" ]

[ "17 - OH progesterone level of 215 ng / ml,", "Detailed investigations ( renal Doppler ultrasound, adrenal CT scan, urinary metanephrine, 11 - Deoxycortisol, plasma renin activity, aldosterone levels and cortisolemia ) failed to detect any cause for secondary hypertension, and a diagnosis of essential hypertension was made", "basal level of 17 - OH progesterone at 12 ng / ml, ACTH of 77 pg / ml ( reference range : 10–50 pg / ml ) and androstenedione of 2.12 nmol / l ( reference range : 0.77–1.82 nmol / l )", "Brain MRI showed bilateral periventricular white matter hyperintensity on T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) images, which is consistent with leukoencephalopathy ( Figs. 1, 2 Fig. 1 T2 - weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity ( arrow ) and cortico - subcortical atrophy. Fig. 2 FLAIR - weighted axial MRI sequence showing bilateral periventricular white matter hyperintensity ( arrow ) located mainly in the posterior regions with agenesis of the corpus callosum. Fig. 3 T1 - weighted sagittal MRI sequence showing complete agenesis of the corpus callosum. ). The lesions predominated in the posterior regions and were associated with cortico - subcortical atrophy ( Figs. 1, 2 ) and complete agenesis of the corpus callosum ( Figs. 1 – 3 )", "Routine blood and urine tests were normal as well as blood tests for liver function, lactate, amino acids, ceruloplasmin, inflammatory markers and urine amino and organic acids. Lumbar puncture revealed normal CSF protein and glucose levels, and neither oligoclonal bands nor evidence of infection were detected. The serum leukocyte activity of Arylsulfatase A was normal. Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative." ]

[ "hypertension" ]

[ "salt - wasting", "acute dehydration, salt loss syndrome", "Two adrenal crises occurred at one and nine years of age", "Autoantibodies to thyroid peroxidase and thyroglobulin as well as antinuclear antibodies were negative" ]

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[ "ophthalmologic were normal" ]

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[ "He was born at term, weighing 2,900 g," ]

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[ "15 - yr - old" ]

[ "40 d old" ]

[ "with salt - wasting 21 - hydroxylase deficiency CAH" ]

[ "hydrocortisone , fludrocortisone and salt" ]

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[ "vomiting and diarrhea" ]

[ "A 33 - year - old G2P1 woman presented to our obstetric unit at 17 weeks ' gestation for antenatal care of her second pregnancy", "Upon reevaluation of family history, however, the parents revealed that their 27 - month - old first baby had been diagnosed with CLAH. The first baby was delivered vaginally at 36 + 2 weeks ' gestation with birth weight 2,360 g. Initial symptoms included projectile vomiting and poor oral intake, with lethargy and hyperpigmentaion 10 weeks after birth. The initial laboratory finding demonstrated hyponatremia ( 125 mEq / L ) and hyperkalemia ( 6.6 mEq / L ). Basal adrenal hormone levels and an adrenocoticotropic hormone ( ACTH ) stimulation test showed a severe deficiency of adrenal hormones ( Table 1 ). Abdominal ultrasonography and computed tomography ( CT ) demonstrated diffusely enlarged adrenal glands with markedly low density. Gene analysis revealed a normal CYP21A2 gene sequence but a homozygous mutation c.772C > T in exon 7 of StAR. She was diagnosed with CLAH and treated with stress doses of hydrocortisone and 1036mineralocorticoid, which were tapered to a maintenance dose", "Four months after birth, the second baby was admitted to our hospital with vomiting and diarrhea after DTaP vaccination" ]

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[ "Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median ( MoM ) with low alpha - fetoprotein ( AFP ) and human chorionic gonadotropin ( hCG ) level, 0.6 MoM and 0.52 MoM, respectively", "karyotype by amniocentesis was 46,XX", "Level II ultrasonography after 21 weeks ' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia", "homozygous c.772C > T substitution resulting in a glycine to stop codon substitution at amino acid 258 ( Fig. 1 )", "Screening for congenital adrenal hyperplasia was normal, 17α - OH progesterone ( 17α - OHP ) 8.33 ng / mL ( normal 1.7 - 25.0 ng / mL )", "laboratory profile was similar to that of her sister, but without enlargement of adrenal glands on ultrasonography", "Genetic evaluation from the peripheral blood confirmed the same mutation" ]

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[ "normal female external genitalia" ]

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[ "G2P1", "17 weeks ' gestation", "second pregnancy", "Maternal serum screening demonstrated a very low estriol level of 0.06 multiples of the median ( MoM ) with low alpha - fetoprotein ( AFP ) and human chorionic gonadotropin ( hCG ) level, 0.6 MoM and 0.52 MoM, respectively", "Level II ultrasonography after 21 weeks ' gestation demonstrated no structural abnormalities including the adrenal glands and genitalia", "A 2,665 g female baby was delivered vaginally with Apgar scores of 7 and 9 at 40 weeks ' gestation" ]

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[ "33 - year - old" ]

[ "Four months after birth" ]

[ "CLAH" ]

[ "treatment of mineralocorticoid and hydrocortisone ." ]

[ "Her height was 110 cm ( 10 - 25th percentile ), weight 23 kg ( 75 - 90th percentile ).", "Her body weight, length and head circumference were 2900, 51 cm and 33.5 cm, all of them were beneath the 5 th percentiles. Her blood pressure was 60/40 mmHg, respiratory rate was 39 / min, pulse rate was 112 / min and body temperature was 37.1 ° C. '" ]

[ "poor weight gain", "without history of vomiting or diarrhea" ]

[ "Orchiectomy", "A 28 - day - old phenotypic female infant was admitted to pediatric endocrinology clinic of Al - Zahra Hospital, affiliated to Isfahan University of Medical Sciences, because of poor weight gain and lethargy. She was a full - term infant with a birth weight of 3250 gr ( 50 th percentile ), length of 51 cm ( 50 th percentile ) and head circumference of 34 cm ( 50 th percentile).The patient had no perinatal problem. She was the 1 st child of nonconsanguineous parents. At the time of admission, she was lethargic without history of vomiting or diarrhea. There was not any familial history of similar presentation or features endocrine disease. She had no history of drug consumption except vitamin A+D." ]

[ "lethargy", "lethargic", "lethargic", "depressed fontanele" ]

[ "Ultrasonographic examination revealed small hypoplastic uterus ( 6 * 7 * 3 ml ) or atretic ovaries and adrenal glands had normal sizes", "normal laboratory results except for 17 OHP which was lower during the period", "Renal Doppler ultrasonography and scan was performed which was normal", "Ultrasonography revealed the testicles in the abdominal cavity and uterus was not detected in pelvis", "Chromosome study showed 46XY pattern", "Na : 142 mmol / l, K : 4.5 mmol / l,17OHP : 0.1 ng / ml, ACTH : 22 pg / ml, Renin:50.8 pg / ml, Aldosterone : 105 pg / ml" ]

[ "high blood pressure", "mild dehydration and decreased skin turgor." ]

[ "adrenal glands had normal sizes", "decreased cortisol level and increased ACTH level", "adrenal insufficiency" ]

[ "small hypoplastic uterus ( 6 * 7 * 3 ml ) or atretic ovaries", "hyponatremia, hyperkalemia", "testicles in the abdominal cavity and uterus was not detected in pelvis", "External genitalia seemed normal female type with no ambiguity" ]

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[ "mild hyperpigmentation, including oral cavity." ]

[ "no hyperpigmentation", "decreased skin turgor.", "mild hyperpigmentation, including oral cavity." ]

[ "full - term infant with a birth weight of 3250 gr ( 50 th percentile ), length of 51 cm ( 50 th percentile ) and head circumference of 34 cm ( 50 th percentile).The patient had no perinatal problem." ]

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[ "28 - day - old" ]

[ "28 - day - old" ]

[ "lipoid CAH" ]

[ "replacement therapy with standard doses of glucocorticoid ( hydrocortisone ) and mineralocorticoid ( fludrocortisone ) and sodium chloride was initiated . After replacement therapy , electrolyte abnormalities were corrected during first week and the patient was discharged from hospital with good clinical condition .", "fludrocortisone and sodium chloride was discontinued and treatment continued with hydrocortisone ." ]

[ "and bleeding gum" ]

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[ "A 14 - year - old girl, visited to outpatient Department of Periodontia, Government Dental College and Hospital, Ahmedabad, India with chief complain of premature loss of deciduous and permanent teeth and mobility in remaining teeth", "History revealed that her deciduous teeth had erupted normally, but exfoliated gradually by the age of 4 - 5 years. Similarly, her permanent teeth were lost prematurely after erupting normally", "periodontal flap surgery", "There was no family history of ichthyosis or hereditary or acquired palmoplanter keratodermas" ]

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[ "serum of the patients showed high immunoglobulin G ( IgG ) titer against A. actinomycetemcomitans. Moreover, A. actinomycetemcomitans colonies were cultured in high percentages from the pocket samples", "serum IgG titers against A. actinomycetemcomitans decreased in the patients", "Orthopantogram showed extensive alveolar bone loss in all remaining teeth. The alveolar bone around the mobile teeth was devoid of definable lamina dura. An extensive alveolar bone loss was noted, giving the teeth 31, 41 and 43 a “ floating in air appearance, ” which were extracted afterwards. Radiographically, right and left lateral oblique radiographs show angular bone loss and periodontal widening present in relation with 36 and 46. There are developing tooth germs of permanent tooth are also seen." ]

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[ "The fingers were pointed giving clawed appearance" ]

[ "edentulous area between teeth 44 and 33 and 11, 21 and 22 were also missing. Edentulous maxillary and mandibular ridges were covered with normal mucosa. The teeth present were 12, 13,14,15,16,22, 24, 25, 26, 33, 34, 35, 36, 44, 45 and 46 covered with soft deposits and band of subgingival calculus. Gingiva was fiery red in color with inflammatory gingival enlargement Iva Ingle Classification grade II. Pathological migration was associated with 12, 14, 23, 24, 33 and 34. On assessment grade III mobility was present in relation with 14, grade II in relation with 24, 25, 33, 34, 36 and 44. Remaining teeth were present with grade I mobility. There was the presence of recession grade III in relation with 14 and 33", "presence of 16, 26, 31, 36, 46, 41 and 53 in the oral cavity. There is grade III recession and grade II mobility in 53. Remaining teeth revealed the presence of soft deposits and grade I mobility", "mobility in relation with some of her deciduous teeth and then early exfoliation of same", "premature loss of deciduous and permanent teeth and mobility in remaining teeth", "deciduous teeth had erupted normally, but exfoliated gradually by the age of 4 - 5 years", "her permanent teeth were lost prematurely after erupting normally.", "mobility and bleeding gum before 2 years" ]

[ "well - demarcated, yellowish, keratotic plaques over the skin of palms and soles extending on to the dorsal surfaces. Skin of both palms and soles was peeling off leaving underlying red shiny area suggestive of keratoderma. Well circumscribed, psoriasiform, erythematous, scaly plaques were also present on the elbows and knees bilaterally along with dystrophy and transverse grooving of the nails", "dry scaly skin of palms and soles", "well - demarcated keratotic plaques over the skin of her palms and soles, extending on to dorsal surfaces were present", "fissures, thickening and flaking in the skin of palms and soles that resulted in peeling off of skin leaving red thin area underneath since age of 3 - 4 years. She had exacerbation and remissions of the skin lesions since early childhood," ]

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[ "14 - year - old" ]

[ "2 years" ]

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[ "normal head circumference for his age" ]

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[ "A 4 - year - male child born from a consanguineous marriage presented to the pediatrics department with complaints of delayed development and a skin ailment since infancy." ]

[ "delayed development", "child attained head holding at 6 months, sitting without support at 1 year age and walking with support at 2 years. Stiffness in lower limbs started in later part of the first year of life with progressive increase up to the time of presentation", "mental retardation, increased tone in both lower limbs, brisk deep tendon reflexes, and bilateral extensor plantar response suggestive of spastic diplegia. Upper limbs did not show any tone or deep tendon reflex abnormalities. There was also evidence of conduction aphasia in the child", "Electroencephalogram ( EEG ) was normal", "The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal. All" ]

[ "Chest radiograph and all routine hematological investigations were normal.", "The MRI showed diffuse and symmetrical high signal intensity on T2W sequence in bilateral deep periventricular white matter in the frontal and parietal lobes and in the corona radiata. These areas were hypointense on T1W sequence. Subcortical U fibers were normal. Ventricles and gray matter of brain, corpus callosum, thalami, brainstem, and cerebellar hemispheres were normal." ]

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[ "Skeletal, dental, eye/ fundus examination and eye or limb movements were normal" ]

[ "dental, eye/ fundus examination and eye or limb movements were normal" ]

[ "skin ailment", "scaly ichthyotic lesions with severe pruritus presently affecting all body parts and which started in late infancy on the face" ]

[ "His birth was at full - term from an uneventful pregnancy." ]

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[ "4 - year - male" ]

[ "since infancy" ]

[ "Sjogren - Larsson syndrome" ]

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[ "mild anemia ( Hb 8.0 g / dl, reticulocyte count 7 % of circulating erythrocytes )", "reddish colored urine.", "red - colored urine", "mild anemia." ]

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[ "A 13 - year - old child, born of consanguineous marriage, presented with photosensitivity and recurrent blistering. The blisters were first noticed by the parents at the age of 4–5 years. The blisters were mostly present on exposed areas and used to heal with scarring. There was no history of a similar problem in the family. There was no history of acute neurological attacks", "A 3 - year - old male child, born of consanguineous marriage, presented with blisters on exposed areas since the age of around 6 months. The blisters used to heal with scars. Since early infancy the mother had noticed reddish colored urine. The child 's mental and physical development had been normal. There was no family history of a similar problem. There was no history of acute attacks." ]

[ "no history of acute neurological attacks", "mental and physical development had been normal." ]

[ "Histopathological examination of an intact bulla revealed the subepidermal location of the blister", "Routine investigations, including liver and renal function tests, were within normal limits except for mild anemia ( Hb 8.0 g / dl, reticulocyte count 7 % of circulating erythrocytes ). ELISA for HIV was negative. PBG was normal in urine. On screening with a spectrophotometer, urinary total porphyrin was 1187 nmol / mmol of creatinine ( normal < 35 nmol / mmol ). Twenty - four - hour urinary levels of uroporphyrin and coproporphyrin were raised. The erythrocytic porphyrins showed a level of 124.3 μg/100 ml ( reference value less than 40 μg/100 ml using the hematofluorometric method ).", "Routine investigations were within normal limits except for mild anemia. The urine did not show increased level of porphobilinogen ( PBG )" ]

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[ "reddish colored urine.", "red - colored urine" ]

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[ "erythrodontia was not spotted with the naked eyes, the teeth revealed a pink - red fluorescence under Wood 's lamp", "teeth were of coppery - red color", "erythrodontia" ]

[ "photosensitivity and recurrent blistering. The blisters were first noticed by the parents at the age of 4–5 years. The blisters were mostly present on exposed areas and used to heal with scarring.", "severe atrophic scars on the face and exposed parts of the extremities, which had resulted in mutilating deformities of the fingers", "Hypertrichosis, pigmentation, and milia formation were also present on the face", "Histopathological examination of an intact bulla revealed the subepidermal location of the blister", "severe photosensitivity, blistering, and hypertrichosis", "mutilation of the fingers", "blisters on exposed areas", "The blisters used to heal with scars.", "face was badly scarred. There was hypertrichosis on the shoulders, arms, and face", "a few intact blisters and crusted lesions on the hands and feet. Atrophic scars were also present on the extremities", "blistering on the exposed areas since early infancy, healing with atrophic scarring" ]

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[ "13 - year - old", "3 - year - old" ]

[ "4–5 years", "around 6 months" ]

[ "A diagnosis of CEP was made ." ]

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[ "Her heart rate was 120 / min and blood pressure was 100/60 mm Hg. She was breathing at a set rate given by ventilator." ]

[ "chronic intermittent abdominal pain, vomiting, and anorexia for three months" ]

[ "A 17 - year - old female patient weighing 35 Kg presented to emergency department with history of chronic intermittent abdominal pain, vomiting, and anorexia for three months, history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness with respiratory distress for one day. She had no history of snakebite, pain chest, poison intake, or blunt injury to neck or abdomen" ]

[ "history of recurrent generalized tonic clonic seizures for 2 days and history of rapidly progressive ascending type of limb weakness", "conscious ( E 4 V T M 1 ) with power of 1/5 in all limbs, plantars were mute, and deep tendon reflexes were absent", "electroencephalography were normal.", "Cerebrospinal fluid analysis was normal.", "Nerve conduction study showed axonal motor neuropathy" ]

[ "Routine baseline workups including hemogram, blood sugars, liver and kidney function, chest X - ray, electrocardiography, electroencephalography were normal", "Cerebrospinal fluid analysis was normal. Urine Watson – Schwartz test was positive for porphobilinogen. Electrolyte screening showed mild hyponatremia ( serum sodium 126 mmol / L ). Serum phosphates and serum potassium were within normal limits. Ultrasonography of abdomen was unremarkable and serum lead levels were within normal limits.", "Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction. Serum calcium ( 10.8 mg / dl ) and phosphorus levels ( 5 mg / dl ) were within normal limits. Tracheal tube aspirate for acid - fast bacilli was negative" ]

[ "postural hypotension, tachycardia, and sweating", "electrocardiography, electroencephalography were normal", "ST segment elevation was noticed on the cardiac monitor and 12 lead ECG was ordered which showed ST segment elevation in lead II. Cardiac enzyme markers were not elevated. Transthoracic echocardiography was done to rule out any cardiac pathology. It showed posterior pericardial calcification with anterior mitral leaflet and papillary muscle calcification and relaxation abnormality around mitral valve suggestive of early pericardial constriction" ]

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[ "respiratory distress" ]

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[ "17 - year - old" ]

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[ "AIP" ]

[ "heme arginate ( 3 mg / kg / day for 4 days )" ]

[ "body weight had decreased ( 3,045 g )" ]

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[ "The girl patient was the first child of unrelated healthy Japanese parents. She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g. She was noticed to have hyperpigmentation and failure to thrive at 14 d, and was referred to our hospital at 27 d of age" ]

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[ "electrolytes were within normal ranges. Endocrinological examination showed a markedly high plasma adrenocorticotropin stimulating hormone ( ACTH ) level ( 3,341 pg / ml ). The serum 17 - hydroxyprogesterone level was normal. On ultrasonography, bilateral adrenal glands were slightly enlarged ( right 1.4 × 1.9 cm, left 1.6 × 1.2 cm )", "The patient had a one base insertion ( 246insG ) as a heterozygous state. Note overlapping signals after the insertion site. ( B-2 ) An arrow indicates the C to T transition. This change substitutes cysteine for arginine at codon 182. ). The patient ’s karyotype was 46, XX" ]

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[ "normal female external genitalia with no ambiguity" ]

[ "normal female external genitalia with no ambiguity" ]

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[ "hyperpigmentation", "remarkable pigmentation" ]

[ "She was delivered at term after an unremarkable gestation through cesarean section because of breech presentation. Her birth weight was 3,184 g." ]

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[ "27 d of age" ]

[ "14 d ," ]

[ "She was diagnosed as having adrenal insufficiency caused by CLAH ." ]

[ "She was treated successfully with hydrocortisone and fludrocortisones" ]

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[ "A 2 - year - old boy was referred to our hospital due to developmental delay, ichthyosis, asthma, and recurrent pneumonia. His parents were related but there was no history of asthma, and allergic disorders in his family, and close relatives. He had ichthyosis at birth, and mild intermittent asthma, and 2 episodes of pneumonia also were observed in his first year of life. He had no history of seizure" ]

[ "developmental delay", "no history of seizure", "spastic diplegia and brisk deep tendon reflexes in lower limbs. He was not able to stand or walk, independently and his speech was limited to 2–3 meaningful words. Acquisition of other developmental skills was mildly delayed with achieving head control and sitting without support at 5 and 12 months, respectively", "Electroencephalography, routine laboratory tests, and chromosomal study were also normal.", "Magnetic resonance imaging ( MRI ) demonstrated high - intensity lesions in the deep white matter around the trigons of lateral ventricles" ]

[ "routine laboratory tests, and chromosomal study were also normal", "Magnetic resonance imaging ( MRI ) demonstrated high - intensity lesions in the deep white matter around the trigons of lateral ventricles (", "Histopathology of the skin biopsy showed hyperkeratosis with keratotic plugging and parakeratosis consistent with ichthyosis. Molecular genetics study utilizing sequencing of the polymerase chain reaction product using the exon - specific primers revealed a c.370 - 372 ( GGA ) deletion mutation in the second exon of ALDH3A2 gene in a homozygote state" ]

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[ "mild intermittent asthma, and 2 episodes of pneumonia" ]

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[ "Funduscopic examination was normal" ]

[ "ichthyosis", "had ichthyosis", "Extensive hyperkeratosis and scaling of the skin were seen particularly in the dorsum of hands, skin flexures, and lower abdomen", "Histopathology of the skin biopsy showed hyperkeratosis with keratotic plugging and parakeratosis consistent with ichthyosis" ]

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[ "2 - year - old" ]

[ "at birth" ]

[ "the diagnosis of SLS was confirmed ." ]

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[ "Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia" ]

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[ "Case one was a 30 - year - old male patient who presented with asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body since the age of 10 years. The initial lesions started in the chest and then spread to the entire body in 2 years. There was no history of photosensitivity or handling of any chemical or any history of drug intake. None of the family members was affected", "Case two was a 22 - year - old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body since 12 years.", "Case three was a 14 - year - old boy who presented with similar lesions all over the body since the age of 2 years. His palms and soles also showed similar mottled pigmentation. He was born to parents of second degree consanguinous marriage. He also had multiple verucca vulgaris over the left arm and dorsum of hands. He had recurrent upper respiratory tract infections and severe growth retardation and mental retardation", "Case four was the 9 - year - old sibling of the 14 - year - old boy who revealed similar lesions all over the body since 9 months of age. Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth.", "Case five was a 21 - year - old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities since the age of 1 - year. There was no family history of similar lesions. His palms and soles were normal. There was no other significant positive history." ]

[ "mental retardation" ]

[ "Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin", "Peripheral blood smear showed a normocytic normochromic blood picture with leucopenia and eosinophilia", "His serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests ( ELISA ) were negative", "Histopathology showed similar features as that of the first case.", "Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer." ]

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[ "recurrent upper respiratory tract infections" ]

[ "severe growth retardation" ]

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[ "asymptomatic multiple hypopigmented, and hyperpigmented skin lesions all over the body", "initial lesions started in the chest and then spread to the entire body in 2 years", "no history of photosensitivity", "skin did not reveal atrophy or telangiectasia. His palms, soles, and mucous membranes were within normal limits. Hair and nails were normal", "Skin biopsy from the hyperpigmented macules showed the increased melanin pigmentation, and the hypopigmented macules showed a marked decrease in the epidermal basal melanin", "asymptomatic multiple hypo and hyperpigmented macules all over the body", "similar lesions all over the body", "palms and soles also showed similar mottled pigmentation", "multiple verucca vulgaris over the left arm and dorsum of hands", "similar lesions all over the body", "Similar lesions were seen in his palms and soles also. He had recurrent pyodermas since birth", "molluscum contagiosum lesions on the face", "Both the siblings also had a broad nasal bridge, long philtrum, and high arched palate", "Both the brothers had hypopigmented, and hyper pigmented macules of varying sizes all over the body", "Histopathology showed similar features as that of the first case", "asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities", "His palms and soles were normal.", "Biopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer" ]

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[ "30 - year - old", "22 - year - old", "9 - year - old", "21 - year - old" ]

[ "age of 1 - year ." ]

[ "a diagnosis of dyschromatosis universalis hereditaria ( DUH ) was made", "diagnosis of DUH was made in all the four cases .", "a diagnosis of dyschromatosis symmetrica hereditaria was made" ]

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[ "Female patient, 55 years old, white, reported the onset of yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas. The lesions started during infancy and were asymptomatic. The patient did not present underlying diseases and denied familial cases of the same malady.", "Female patient, 48 years old, white, reported the onset of yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae. In her personal records, a past history of arterial hypertension was noticed. The patient denied similar cases in her family." ]

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[ "The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers", "echocardiogram were normal.", "The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis", "normal electrocardiogram and echocardiogram )" ]

[ "Cardiovascular evaluation did not identify changes and the electrocardiogram and echocardiogram were normal", "arterial hypertension", "Cardiological evaluation did not show changes ( normal electrocardiogram and echocardiogram )" ]

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[ "Right ophthalmoscopy, retinography and angiography revealed angioid streaks", "Right ophthalmoscopy identified the presence of angioid streaks, confirmed by retinography and angiography" ]

[ "yellowish papules, initially in the cervical region, with progression to the cubital and popliteal fossae, inguinal and periumbilical areas.", "grouped yellowish papules were visualized, forming plaques in all of the cervical region, cubital fossae, right popliteal fossa, bilateral and periumbilical inguinal region", "The histological examination revealed calcification and fragmentation of elastic fibers in the middle and deep dermal layers", "yellowish asymptomatic micropapules in the cervical region five years ago, which later progressed to the axillae and cubital fossae.", "coalescent yellowish papules forming plaques distributed symmetrically in the cervical region, axillas and cubital fossae", "The anatomopathological examination made evident calcified, distorted and fragmented elastic fibers in the dermis," ]

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[ "55 years old" ]

[ "The lesions started during infancy" ]

[ "pseudoxanthoma elasticum", "pseudoxanthoma elasticum" ]

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[ "Body weight was 8.8 kg ( 3 to 10 percentile ) in patient A, 9.4 kg ( 10 to 25 percentile ) in patient B, body length was 73.7 cm ( 3 to 10 percentile ) in patient A, 75.4 cm ( 10 to 25 percentile ) in patient B at 14 months of age." ]

[ "poor oral intake, vomiting, lethargy and dehydration" ]

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[ "normal development" ]

[ "slightly elevated potassium level and low level of sodium without severe adrenal insufficiency symptoms before discharge from neonatal intensive care unit ( NICU ). The tandem mass spectrometry screening for congenital metabolic disease were normal including 17 - OHP for congenital adrenal hyperplasia. The endocrinologic investigations including serum ACTH and cortisol were performed in both patients because of hyperpigmentation, mild electrolyte abnormalities although both patients did not show the severe adrenal insufficiency symptoms. Laboratory findings revealed normal 17 - OHP, elevated ACTH ( A, 4,379.2 pg / mL at 23 days of life; B, 11,616.1 pg / mL at 29 days of life ), and high plasma renin activity ( A, 49.02 ng / mL / hr; B, 52.7 ng / mL / hr ). However, the level of plasma cortisol before treatment were normal ( 8.71 µg / dL initially, 7.11 µg / dL in 2nd sample ) in patient A, but low ( 1.5 µg / dL ) in patient B. The results of endocrinologic investigation are shown in Table 1. The enlargement adrenal glands in both patients were not remarkable on the abdominal ultrasound soon after birth. Moreover, hyperplasia of the adrenal glands was not observed on abdominal computed tomography ( CT ) performed at 11 months of age in both patients. Patient A showed slightly decreased to normal sodium level ( 132 to 139 mmol / L ) not to need sodium supplementation during hospitalization and she was discharged from NICU at 22 days of age. Discharge of patient B was delayed for correction of hyponatremia ( 129 to 133 mmo / L )", "Chromosome analysis of both patients revealed normal 46, XX karyotype. The result of gene analysis of StAR revealed a heterozygous condition for c.544C > T ( p. R182C ) in exon 5 and c.722C > T ( p. Q258X ) in exon 7" ]

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[ "slightly elevated potassium level and low level of sodium", "The endocrinologic investigations including serum ACTH and cortisol were performed in both patients because of hyperpigmentation, mild electrolyte abnormalities although both patients did not show the severe adrenal insufficiency symptoms. Laboratory findings revealed normal 17 - OHP, elevated ACTH ( A, 4,379.2 pg / mL at 23 days of life; B, 11,616.1 pg / mL at 29 days of life ), and high plasma renin activity ( A, 49.02 ng / mL / hr; B, 52.7 ng / mL / hr ). However, the level of plasma cortisol before treatment were normal ( 8.71 µg / dL initially, 7.11 µg / dL in 2nd sample ) in patient A, but low ( 1.5 µg / dL ) in patient B.", "The enlargement adrenal glands in both patients were not remarkable on the abdominal ultrasound soon after birth. Moreover, hyperplasia of the adrenal glands was not observed on abdominal computed tomography ( CT ) performed at 11 months of age in both patients.", "slightly decreased to normal sodium level ( 132 to 139 mmol / L )", "hyponatremia ( 129 to 133 mmo / L )", "adrenal insufficiency symptoms of poor oral intake, vomiting, lethargy and dehydration", "retarded physical growth" ]

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[ "desaturation and tachypnea." ]

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[ "hyperpigmentation", "skin hyperpigmentation" ]

[ "Phenotypic female twins ( A, B ) were born at 36 + 2 gestational week to unrelated parents. Apgar scores were 8 at 1 minute and 9 at 5 minutes in both patients. Birth weight was 1,920 g ( < 10 percentile ) in A and 2,040 g ( 10 to 25 percentile ) in B, height was 43 cm ( 10 to 25 percentile ) in A and 44 cm ( 10 to 25 percentile ) in B. Patient A needed the oxygen supplementation with hood and nasal prong for 3 days due to desaturation and tachypnea. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium without severe adrenal insufficiency symptoms before discharge from neonatal intensive care unit ( NICU )" ]

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[ "14 months of age ." ]

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[ "CLAH" ]

[ "Patient B started corticosteroid supplementation before manifestation of severe salt losing symptoms , except hyponatremia", "steroid supplementation ( fludrocortisones 0.2 mg daily in 2 divided doses , and hydrocortisone 12 mg daily in 3 divided doses ) at 14 months of age" ]

[ "Coagulopathy was also detected", "height was 42 cm ( < 3rd percentile ), her weight was 2.9 kg ( < 3rd percentile ), and her head circumference was 33.5 cm ( < 3rd percentile", "white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g / dL and a thrombocyte count of 93,000/µL.", "The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng / mL ( normal values are 14.0 - 647.2 ng / mL ), and the transferrin saturation was 97.2 %", "coagulopathy", "her vital signs were unstable", "Active gastrointestinal bleeding" ]

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[ "A two - month - old female infant was transferred to Seoul National University Children 's Hospital with abdominal distension and hyperbilirubinemia. She was born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg ( < 3rd percentile ). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly. She had no familial medical history of gastrointestinal or hepatobiliary diseases. The patient 's older brother was healthy and had experienced no medical problems. Her mother denied having any history of stillbirth or abortion" ]

[ "neurological development was delayed", "brain MRI and chromosomal study produced normal findings." ]

[ "aspartate aminotransferase ( AST ), 176 U / L; alanine aminotransferase ( ALT ), 106 U / L; total bilirubin, 1.76 mg / dL; and direct bilirubin, 1.2 mg / dL. Toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes simplex virus and hepatitis B viral markers were examined under the suspicion of neonatal hepatitis, but all results were non - diagnostic. Abdominal sonography was performed to exclude biliary atresia, but there was no specific finding in the hepatobiliary tract.", "When the infant was 50 days old, a small amount of ascites was noted, and bilirubin levels had increased to a total serum bilirubin level of 10.89 mg / dL and a direct bilirubin level of 9.61 mg / dL. Coagulopathy was also detected. The amount of ascites increased thereafter, and ascites tapping was performed. The serum - ascites - albumin gradient level was elevated,", "The initial laboratory examination showed a white blood cell count of 13,600/µL, a hemoglobin level of 10.1 g / dL and a thrombocyte count of 93,000/µL. The liver function laboratory studies showed a total serum bilirubin level of 8.4 mg / dL, a direct bilirubin level of 6.4 mg / dL, an AST level of 225 U / L and an ALT level of 114 U / L. The albumin level was 2.4 g / dL, and the ammonia level was increased to 149 µg / dL. The prothrombin time was 31.2 seconds, and the international normalized ratio was 3.02. The serum ferritin level was elevated to 1,181.38 ng / mL ( normal values are 14.0 - 647.2 ng / mL ), and the transferrin saturation was 97.2 %. The serum alpha - fetoprotein level was in the high normal range ( 19,737.27 ng / mL; normal values are 40 - 19,953 ng / mL ). Tyrosine was elevated in the plasma amino acid studies. However, no succinylacetone peak was found in the urine organic acid studies, which excluded the diagnosis of tyrosinemia. Abdominal magnetic resonance imaging ( MRI ) verified a diffuse heterogeneous low signal intensity in the liver on T2 - weighted images, suggesting iron deposition ( Fig. 1 ). An oral mucosal biopsy was performed to detect extra - hepatic siderosis, but adequate submucosal gland tissues could not be obtained. All of the studies performed to evaluate metabolic diseases presented non - diagnostic findings.", "The pathological findings, which are presented in Fig. 2, revealed diffuse parenchymal iron deposition in the liver with iron staining; these findings were consistent with NH and distinct from mesenchymal iron deposition in cases of excessive iron supply. The studies also revealed diffuse parenchymal collapse and occasional nodular regeneration, sinusoidal collagen accumulation and fibrosis, intracytoplasmic and intracanalicular cholestasis, and a decreased number of bile ducts with hematoxylin and eosin staining.", "Assessments by brain MRI and chromosomal study produced normal findings. \"" ]

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[ "hypoglycemia" ]

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[ "whole - body jaundice" ]

[ "born at 36 weeks 2 days of gestation via a normal spontaneous vaginal delivery and had a birth weight of 1.27 kg ( < 3rd percentile ). Her Apgar scores were 6 at 1 minute and 9 at 5 minutes. Because she was small for her gestational age, she was admitted to the neonatal intensive care unit immediately after birth. Initially, hypoglycemia was noted and dextrose fluid was administered. Antenatal sonography findings presented no evidence of fetal hydrops or hepatomegaly." ]

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[ "two - month - old" ]

[ "birth" ]

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[ "We report a case of a 40 - year - old man with CAH/21 - hydroxylase deficiency, who willingly interrupted Prednisolone therapy for years. In 2007 his left adrenal gland was removed and diagnosed with adrenocortical carcinomabilateral orchiectomy", "surgical removal of his right adrenal gland" ]

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[ "Serum hormonal screening showed high 17 - OH progesterone and ACTH", "Serum tumor markers at 12.09.2013 : AFP 10.56 IU / mL ( AFP 4.03 IU / mL 01.2012 ), hGT beta and CEA – not elevated, semen analyses : azoospermia.", "Gross findings : right testicle 2.5/2.5/2.5 cm, left – 3.5/2/2 cm, with brown firm cut surface, lobulated and septated by yellow folds ( 0.1–1.5 cm ). The microscopic examination showed complete replacement of the normal testicular tissue by sheets and nests of large bizarre mono- and multinucleated cells, large nuclei with prominent nucleoli, abundant eosinophilic cytoplasm with lipochrome pigments ( Fig. 3 ). Nests of cells were separated by fibrous septs. Only the epididymis and a thin band of atrophic testicular parenchyma were preserved. The tumor cells did not express CD 117, PLAP, CK. Melan A and inhibin - α were positive in 50 % of the cells. There were no mitotic figures on HE - staining ( Ki 67 negative ). No vascular invasion and tumor emboli were found. The spermatic cord and tunica vaginalis were not infiltrated.", "In the left adrenal gland we found polygonal cells with mild nuclear pleomorphism, conspicuous nucleoli, abundant eosinophilic granular cytoplasm, some with lipochrome pigments, without mitotic activity ( Ki 67 positive in < 1 % of nuclei ). The clear cell component was about 26 %. In CAH, marked diffuse hyperplasia of zona fasciculata is a result of ACTH stimulation. There is also a conversion of zona fasciculata cells into zona reticularis - type cells ( lipid - depleted ). The cells exhibited strong positive expression for vimentin, Melan A and inhibin. In the right adrenal gland microscopically we found fields and circumscribed but nonencapsulated nodules that protruded into the adjacent fat, consisting of fasciculata - type cells and nodules composed of zona reticularis - type cells with lipofuscin. Nuclear and cellular pleomorphism was more prominent than in the left adrenal gland. Mitoses necrosis, hemorrhage, sinusoidal, vascular and capsular invasion were not found. The required number of morphological criteria, according to Weiss and Aubert, to classify the lesion as carcinoma, were not met" ]

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[ "bilateral testicular masses", "semen analyses : azoospermia", "frozen sections were interpreted as malignant tumors. Gross findings : right testicle 2.5/2.5/2.5 cm, left – 3.5/2/2 cm, with brown firm cut surface, lobulated and septated by yellow folds ( 0.1–1.5 cm ). The microscopic examination showed complete replacement of the normal testicular tissue by sheets and nests of large bizarre mono- and multinucleated cells, large nuclei with prominent nucleoli, abundant eosinophilic cytoplasm with lipochrome pigments ( Fig. 3 ). Nests of cells were separated by fibrous septs. Only the epididymis and a thin band of atrophic testicular parenchyma were preserved. The tumor cells did not express CD 117, PLAP, CK. Melan A and inhibin - α were positive in 50 % of the cells. There were no mitotic figures on HE - staining ( Ki 67 negative ). No vascular invasion and tumor emboli were found. The spermatic cord and tunica vaginalis were not infiltrated." ]

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[ "40 - year - old" ]

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[ "CAH/21 - hydroxylase deficiency", "TARTs", "CAH bilateral adrenal cortical hyperplasia of a diffuse and nodular type with multiple bilateral cortical nodules , pigmented nodules and congenital adrenal cytomegaly and bilateral TARTs revealing morphologically similar changes" ]

[ "Prednisolone" ]

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[ "A 6 - year - old male child, first born of third - degree consanguineous parents, presented with scaly lesions on skin over both upper and lower limbs since day 5 of life, global developmental delay and stiffness of all limbs. The child was delivered by cesarean section. He was admitted in neonatal intensive care unit for neonatal jaundice. He had recurrent episodes of generalized tonic clonic seizures since the age of 1½ years with a total of 8 episodes so far ( last episode at the age of 4 years )." ]

[ "global developmental delay and stiffness of all limbs", "recurrent episodes of generalized tonic clonic seizures since the age of 1½ years with a total of 8 episodes so far ( last episode at the age of 4 years ).", "global developmental delay. He is not able to stand till date. He is able to speak only monosyllables and obeys simple commands. Central nervous system motor examination showed spasticity, reduced power ( 3/5 in lower limbs and 4/5 in upper limbs ), exaggerated deep tendon reflexes of all four limbs, and bilateral plantar extensor. Cranial nerve examination was normal. There was no sensory deficit or cerebellar signs", "mental retardation and spastic diplegia" ]

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[ "Kyphoscoliosis of trunk was present" ]

[ "Eye examination revealed ectropion, mildly congested conjunctiva, and small opacity in the cornea at 8 o’clock position. Fundus examination revealed glistening spots in the foveal and parafoveal region" ]

[ "scaly lesions on skin over both upper and lower limbs since day 5 of life,", "diffuse large brown colored diamond shaped adherent scales were present over the skin of all limbs implicating generalized ichthyosis with relative sparing of face. Seborrheic dermatitis of scalp was present. Diffuse hyperpigmented macules were present over the flexural areas and abdominal skin", "congenital ichthyosis" ]

[ "delivered by cesarean section. He was admitted in neonatal intensive care unit for neonatal jaundice" ]

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[ "6 - year - old" ]

[ "day 5 of life" ]

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[ "red colored urine for the past 1 year.", "hemoglobin, 9.8 g / dL, platelets and white blood cell counts were normal. Peripheral blood smear showed normocytic red blood cells. Liver function test showed a moderate increase in lactic dehydrogenase ( 423U / l ) and mild increase in serum bilirubin ( 1.8 mg / dL )", "splenomegaly ( 17 mm )" ]

[ "no history of acute abdominal pain" ]

[ "A 27 - year - old male, presented to our clinic with a history of foreign body sensation in both eyes for the previous 2 years. He had a history of blistering skin lesions on the photo - exposed areas of the body for the past 12 years" ]

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[ "Hematological tests reported hemoglobin, 9.8 g / dL, platelets and white blood cell counts were normal. Peripheral blood smear showed normocytic red blood cells. Liver function test showed a moderate increase in lactic dehydrogenase ( 423U / l ) and mild increase in serum bilirubin ( 1.8 mg / dL )", "Ultrasonography of the whole abdomen showed splenomegaly ( 17 mm )" ]

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[ "red colored urine for the past 1 year" ]

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[ "severe pain in the fingers of both hands 1 - year prior presentation", "resorption of distal phalanges of all the fingers in both hands" ]

[ "foreign body sensation in both eyes for the previous 2 years", "The patient 's uncorrected visual acuity was 20/40 in both eyes. Best corrected visual acuity was 20/20 in both eyes with a correction of – 0.5 × 115 ° in the right eye and – 1.25 × 80 ° in the left eye. Air - puff tonometry measured intraocular pressure of 14 mm - Hg bilaterally. The fundus examination was unremarkable. Slit - lamp examination indicated scleral necrosis in the interpalpebral area of both eyes that was more pronounced temporally compared to nasally. Temporally, it was 4 mm × 3 mm in the left eye and 3 mm × 3 mm in the right eye. Nasally, minimal scleral necrosis was seen with overlying fibrosed conjunctiva in both eyes. Mild conjunctival scarring was present in the temporal necrosed part of the right eye. In the left eye, the temporal necrosed part was devoid of conjunctival tissue, a frill of conjunctival tissue was present at the margin of the necrosed area. Conjunctiva and sclera in the covered area appeared to be normal. Infiltrations were seen in the peripheral cornea of both eyes near the limbus with temporal and nasal involvement. Fluorescein staining indicated normal epithelium. Schirmer 's test 1 was 8 mm in the right eye and 10 mm in the left eye" ]

[ "history of blistering skin lesions on the photo - exposed areas of the body for the past 12 years. At first, blisters started developing over the lower extremities and then gradually involved upper extremities and face. There was also a history of hyper - pigmentation and scarring of the photo - exposed areas of the body", "pinched up nose, scarring over the lips, nose, hands", "onycholysis of the smallest digits. Onycholysis was present on all the toes" ]

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[ "27 - year - old" ]

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[ "The treatment involved complete avoidance of sunlight and use of dark goggles ." ]

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[ "clitoral resection and vaginoplasty" ]

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[ "high testosterone level, raised 17 - hydroxyprogeterone level", "normal karyotype ( 46, XX )", "The first trimester screening conducted at the first visit of 12 + 3 week of gestation was normal and quad test conducted at 16 + 3 week of gestation was also normal.", "blood sugar was mildly increased than normal range in the 100 g oral glucose tolerance test conducted at 24 + 6 week of gestation", "Ultrasonography was performed at two to four weeks. The development of fetus was appropriate to the gestational age without any sign of intrauterine growth retardation or large for gestational age", "mildly increased level of blood sugar at the 100 g oral glucose tolerance test conducted at 23 + 4 week of gestation" ]

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[ "enlarged clitoris", "gestational diabetes mellitus", "gestational diabetes mellitus" ]

[ "enlarged clitoris" ]

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[ "got pregnant spontaneously without any trial of assisted reproductive technology", "The first trimester screening conducted at the first visit of 12 + 3 week of gestation was normal and quad test conducted at 16 + 3 week of gestation was also normal", "She was diagnosed with gestational diabetes mellitus as blood sugar was mildly increased than normal range in the 100 g oral glucose tolerance test conducted at 24 + 6 week of gestation", "Ultrasonography was performed at two to four weeks. The development of fetus was appropriate to the gestational age without any sign of intrauterine growth retardation or large for gestational age", "Cesarean section was preferred other than vaginal delivery, as she had cephalopelvic disproportion on examination and history of vaginoplasty. She delivered female weighs 2,990 g by elective cesarean section at 38 + 4 week of gestation. The baby exhibited normal 7 Apgar score and did not require oxygen or respiratory assistance. The external genitalia was normal and there was a sign of normal karyotype ( 46, XX ) in the result of chromosomal study", "After one time of spontaneous abortion, 3 years later, at the age of 30, she became pregnant of the second baby spontaneously. She was diagnosed with gestational diabetes mellitus due to the mildly increased level of blood sugar at the 100 g oral glucose tolerance test conducted at 23 + 4 week of gestation", "The development of fetus was appropriate to the gestational age and antenatal care did not show any particular sign", "She delivered 3,250 g female baby at 38 + 2 week of gestation, by cesarean section. The baby exhibited normal Apgar score and did not require oxygen or respiratory assistance" ]

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[ "27 - year - old" ]

[ "eleven years old" ]

[ "a diagnosed case of 21 - hydroxylase deficient simple virilizing form of classic CAH" ]

[ "dexamethasone ( minimum dose 0.5 mg / day to maximum dose 1.0 mg / day )", "changed to prednisolone and the endocrinology department had prescribed it ( minimum dose 10 mg / day to maximum dose 20 mg / day ) before pregnancy ." ]

[ "hemoglobin level of 13.1 g / dL; white blood cell count, 17,800 / mm 3; platelet count, 553,000 / mm 3" ]

[ "abdominal discomfort, diarrhea and weight loss", "cachectic and his abdomen slightly distended with shifting dullness", "diarrhea more than 10 times daily", "protracted diarrhea,", "marked improvement of the diarrhea", "abdominal pain" ]

[ "A 56 - year - old man, who had been a heavy drinker, presented symptoms of general weakness, abdominal discomfort, diarrhea and weight loss and was admitted to the hospital." ]

[ "general weakness,", "depressed and agitated", "mental change" ]

[ "Laboratory examination revealed a hemoglobin level of 13.1 g / dL; white blood cell count, 17,800 / mm 3; platelet count, 553,000 / mm 3; albumin, 2.6 g / dL; total bilirubin, 0.3 mg / dL; GOT, 48 IU / L; GPT, 22 IU / L; and alkaline phosphatase, 117 IU / L. His serum amylase was 856 IU / L and serum lipase 1,077 IU / L.", "computed tomographic ( CT ) scan of the abdomen ( Figure 1 ) revealed evidence of acute exacerbated, chronic pancreatitis, including pseudocysts, one of which was approximately 7 cm in diameter and was located in the tail of the pancreas with adjacent splenic vein occlusion. In addition, right portal vein occlusion, with corresponding perfusion defect and liver infarction, was noted", "His serum zinc level was found to have fallen to 17.4 μ g / dL ( normal range, 70 to 150 μ g / dL )", "A repeat CT scan 10 days later showed total collapse of the pseudocyst and resolution of the PVT and liver infarction" ]

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[ "multiple skin lesions", "skin lesions were vesiculopustular and erythematous eruptions with scales on the face ( Figure 2A ) and perineal areas. During the following week, the lesions spread to involve the hands and feet", "typical skin lesions", "skin lesions began to alleviate", "By this time, his skin lesions had almost healed" ]

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[ "56 - year - old" ]

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[ "we initiated therapy with zinc sulfate at 5 mg daily . Three to four days of zinc supplementation produced marked improvement of the diarrhea and , after one week of zinc supplementation , the skin lesions began to alleviate ." ]

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[ "A one - and - half year old boy presented with generalized scaling over whole body and redness over both cheeks. There was a history of consanguineous marriage and prolonged labor and baby was delivered by normal vaginal delivery. The birth weight of the baby was 2.3 kg and the length of the baby was 36 cm. There was no history suggestive of collodion membrane. Scaling started from 3 weeks of age and had a history of exacerbation in the winter and improvement in summer. Immunization was completed according to the immunization schedule. There was no family history of similar kind of illness. There was no history of any drug intake prior to the scaling or atopic diathesis." ]

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[ "Blood investigations, chest X - ray, urine examination showed no abnormality", "Histopathological examination was done which revealed mild hyperkeratosis" ]

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[ "Left - sided cryptorchidism was present", "cryptorchidism" ]

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[ "no abnormality in the eyes except mild ectropion. There was no evidence of seborrheic blepharitis", "Ophthalmological examination was done and no abnormality found" ]

[ "generalized scaling over whole body and redness over both cheeks.", "no history suggestive of collodion membrane. Scaling started from 3 weeks of age and had a history of exacerbation in the winter and improvement in summer", "fine white to brown scaling over the whole body without any spared area with glistening surface over palms and soles with involvement of flexures. On the scalp fine whitish - grey and grayish brown scaling was present and in some areas there was thick crusting which on removal revealed a moistened surface. On the frontal scalp margin, there were large grayish - brown ichthyotic scales. Both the cheeks were erythematous along with scaling and scales also involved the upper eyelid, upper lips and over the nose", "Histopathological examination was done which revealed mild hyperkeratosis", "generalized scaling with flexural involvement" ]

[ "prolonged labor and baby was delivered by normal vaginal delivery. The birth weight of the baby was 2.3 kg and the length of the baby was 36 cm. There was no history suggestive of collodion membrane", "prolonged labor" ]

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[ "one - and - half year old" ]

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[ "65 kg weight, 160 cm height and 116/82 blood pressure" ]

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[ "born of a non - consanguineous marriage following a full term normal vaginal delivery." ]

[ "average intelligence and had no persistent aggressive, violent or criminal tendencies" ]

[ "Karyotyping showed 46XX pattern", "Ultrasound revealed normal female internal genitalia and adrenals. Magnetic resonance imaging brain and chest X - ray were normal", "Electrolytes, liver function test, lipid profile, thyroid function test, insulin, prolactin, follicle stimulating hormone, luteinizing hormone, estrogen, cortisol were within the normal limit. 17 - OH progesterone and dehydro - epiandrosteine were elevated and showed complete suppression with low dose dexamethasone suppression test" ]

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[ "gain weight, developed hirsutism and never attained menarche", "External body habitus was of male and external genitalia was of female", "no apparent cushingoid features", "normal female internal genitalia and adrenals", "thyroid function test, insulin, prolactin, follicle stimulating hormone, luteinizing hormone, estrogen, cortisol were within the normal limit. 17 - OH progesterone and dehydro - epiandrosteine were elevated and showed complete suppression with low dose dexamethasone suppression test" ]

[ "never attained menarche", "external genitalia was of female", "normal female internal genitalia" ]

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[ "Mother had to frequently remove patient 's facial hairs by hair removing cream" ]

[ "full term normal vaginal delivery" ]

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[ "21 - year old" ]

[ "early childhood" ]

[ "non - classical congenital adrenal hyperplasia ." ]

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[ "weight loss,", "abdominal pain", "no symptoms such as abdominal pain" ]

[ "A 37 - year - old male was admitted with dyspnea, fever, weight loss, cough, sweating, paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea, and abdominal pain. He was diagnosed as having AIP 5 years ago. Moreover, he was an intravenous ( IV ) drug abuser that required a permanent indwelling venous catheter for his repeated attacks" ]

[ "no symptoms such as abdominal pain, dark urine, and neurologic deficit." ]

[ "chest computed tomography revealed multiple cavities in both lungs", "A large mobile veg on anterior leaflet of tricuspid valve commissure ( TVC ) with severe TR was also demonstrated in his transthoracic echocardiography" ]

[ "paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea" ]

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[ "no symptoms such as abdominal pain, dark urine" ]

[ "dyspnea", "cough", "paroxysmal nocturnal dyspnea, exertional dyspnea, orthopnea", "multiple cavities in both lungs" ]

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[ "sweating" ]

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[ "37 - year - old" ]

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[ "He was diagnosed as having AIP 5 years ago ." ]

[ "parenteral carbohydrate as dextrose 50 % to prevent AIP attack" ]

[ "height is 141 cm, weight 47 kg", "blood pressure ( BP ) was normal", "normal BP" ]

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[ "A 25 - year - old female diagnosed as mosaic Turner syndrome was referred to our institution for primary infertility work up.", "She underwent clitoroplasty at 21 years of age" ]

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[ "Her karyotype was reported as 45, X{20}/46, XX{80 },", "17 - hydroxy progesterone ( 17 - OHP ) level was 1.3 ng / ml ( 0.2–1.4 ng / ml ), cortisol ( AM ) was 5–6 μg / dl ( 3.7–9.5 μg / dl ) dehydroepiandrosterone sulfate ( DHEAS ) was 189.6 μg / dl ( 65–380 μg / dl ) and serum total testosterone was 318 μg / dl ( 20–130 μg / dl ) which was highly raised", "transvaginal sonography, uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count", "Her fasting glucose, follicle stimulating hormone ( FSH ), luteinizing hormone ( LH ), thyroid stimulating hormone, and prolactin levels were within normal limits", "karyotype and did the analysis at our own genetics laboratory; where more than 100 metaphases were counted with an automatic scanner and all the metaphases showed 46, XX", "normal levels of 17 - OHP, Cortisol, FSH, LH, but increased levels of testosterone", "adrenocorticotropic hormone ( ACTH ) stimulation test was done, which showed basal plasma 17 - OHP as 2300 ng / dl and postsynacthen ( 60 min ) as 3400 ng / dl ( < 900 ng / dl )" ]

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[ "primary amenorrhea since 16 years of age.", "developed facial hair when she was 8 - year - old. There was hair growth in the chest region. Her voice became hoarse and also there was a gradual enlargement of the clitoris", "not being able to achieve menarche.", "17 - hydroxy progesterone ( 17 - OHP ) level was 1.3 ng / ml ( 0.2–1.4 ng / ml ), cortisol ( AM ) was 5–6 μg / dl ( 3.7–9.5 μg / dl ) dehydroepiandrosterone sulfate ( DHEAS ) was 189.6 μg / dl ( 65–380 μg / dl ) and serum total testosterone was 318 μg / dl ( 20–130 μg / dl ) which was highly raised.", "short stature", "hirsutism was evident. Her simplified Ferriman – Gallwey score for hirsutism was 9 ( ≥3 ). She had underdeveloped breast ( Tanner stage II )", "Her fasting glucose, follicle stimulating hormone ( FSH ), luteinizing hormone ( LH ), thyroid stimulating hormone, and prolactin levels were within normal limits", "Virilizing features of pubertal onset with raised testosterone levels", "features of virilization; normal levels of 17 - OHP, Cortisol, FSH, LH, but increased levels of testosterone" ]

[ "gradual enlargement of the clitoris.", "vagina and cervix were healthy, the clitoris was looking normal ( clitoroplasty done in past ) and urethra was mildly displaced posteriorly", "uterus measured 6 cm × 3 cm × 3 cm; both the ovaries were normal size with good antral follicular count", "hypoplastic uterus and normal ovaries, no palpable gonads in inguinal region" ]

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[ "short stature" ]

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[ "developed facial hair when she was 8 - year - old. There was hair growth in the chest region", "hirsutism was evident. Her simplified Ferriman – Gallwey score for hirsutism was 9 ( ≥3 )." ]

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[ "25 - year - old" ]

[ "8 - year - old ." ]

[ "the diagnosis of NCAH was reached" ]

[ "She was started on low dose steroids to suppress the adrenal production of androgens ." ]

[ "144 cm in height" ]

[ "history of chronic intractable diarrhea" ]

[ "A 19 year old boy presented with bilateral slow growing and painful swellings of his achilles tendons of 4 year duration", "he had surgery for bilateral juvenile cataracts at the age of 8, along with history of chronic intractable diarrhea. He was coherent and co - operative but slow cerebrated with low intelligence. There were no central nervous system symptoms like convulsions, abnormal gait or incoordination of movements. Family history revealed that he was a child of a consanguineous marriage. Other sibling, a girl was normal.", "We find such a rare and perplexing case in a 19 year boy who presented with painful swellings of both achilles tendons causing signification limitation of walking distance" ]

[ "He was coherent and co - operative but slow cerebrated with low intelligence. There were no central nervous system symptoms like convulsions, abnormal gait or incoordination of movements", "achieved complete improvement in his mental status" ]

[ "Initial radiographs of both ankles showed homogenous soft tissue shadow in the lower halves of tendoachilles ( Fig. 3 ). Magnetic resonance imaging showed localized homogenous hyper intense signals with fusiform swellings of tendoachilles", "Biopsy of the excised specimen revealed it to be a xanthoma characterized by the accumulation of mononuclear cells with foamy cytoplasm and multinucleated giant cells with high concentration of cholestanol", "Hematological and biochemical investigations including liver function tests, lipid profile, thyroid function tests and ultrasound examination of abdomen were normal. A special test - serum cholestanol level was elevated to 4.37 mg / dL ( normal value : 0.02 - 0.12 mg / dL )", "normal values of serum cholestanol" ]

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[ "bilateral slow growing and painful swellings of his achilles tendons", "each swelling was of size 5×2 cm, firm, nodular, tender and localized to the distal portion of the tendoachilles just above its insertion point to the calcaneal tuberosity ( Fig. 2 ). He was more symptomatic on the right side", "significant disability with limitation of his walking distance", "Initial radiographs of both ankles showed homogenous soft tissue shadow in the lower halves of tendoachilles ( Fig. 3 ). Magnetic resonance imaging showed localized homogenous hyper intense signals with fusiform swellings of tendoachilles", "Biopsy of the excised specimen revealed it to be a xanthoma characterized by the accumulation of mononuclear cells with foamy cytoplasm and multinucleated giant cells with high concentration of cholestanol", "short statured", "pain on the left ( non - operated ) tendoachilles disappeared completely although swelling persisted. His walking distance improved. However, had reappearance of the swelling in the reconstructed tendon on the right side, although was not painful", "swellings of both achilles tendons causing signification limitation of walking distance" ]

[ "surgery for bilateral juvenile cataracts at the age of 8,", "peculiar yellow conjunctiva" ]

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[ "19 year old", "19 year" ]

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[ "Thus a diagnosis of cerebro - tendinous xanthomatosis was made", "cerebro - tendinous xanthomatosis", "cerebrotendinous xanthomatosis" ]

[ "medical therapy with chenodeoxycholic acid ( CDCA ) , a synthetic bile acid ." ]

[ "red colored urine since birth,", "height 133 cm ( < −3 standard deviations", "anemia an Hb of 8.3 g / dl, with peripheral blood smear revealing microcytic hypochromic anemia with anisopoikilocytosis", "fluorescent red urine" ]

[ "protuberant abdomen with hepatosplenomegaly", "hepatomegaly, splenomegaly" ]

[ "A 13 - year - old male child born off a consanguineous marriage presented with complaints of red colored urine since birth, reddish brown - pigmented teeth, and excessive facial hair since 6 months of age. He also had a burning sensation and recurrent blistering over the sun - exposed areas, which healed with scarring and disfigurement of nails since 1 - year of age. His birth and mental developmental history were normal. He had an asymptomatic female sibling 8 years of age, and there was no family history of similar complaints" ]

[ "mental developmental history were normal" ]

[ "Investigations revealed anemia an Hb of 8.3 g / dl, with peripheral blood smear revealing microcytic hypochromic anemia with anisopoikilocytosis. Urine was port wine color, which fluoresced in Wood 's lamp. Porphobilinogen was not detected on Watson – Schwartz test in the urine", "Ultrasonography of abdomen confirmed the hepatomegaly, splenomegaly, and the undescended testes with hydrocele on the right side", "The affected child exhibited a missense mutation in the UROS gene identified as a transversion of A to G at nucleotide 56, resulting in a substitution of tyrosine by cysteine. The patient showed a homozygous mutant profile, and the parents were heterozygous carriers for the mutation", "absence of porphobilinogen in urine, and a demonstrated mutation of the UROS gene" ]

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[ "red colored urine since birth", "undescended testis on the left side", "undescended testes with hydrocele on the right side", "fluorescent red urine" ]

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[ "short statured" ]

[ "reddish brown - pigmented teeth", "Teeth showed brownish - red pigmentation, fluorescent under Wood 's lamp", "erythrodontia" ]

[ "excessive facial hair", "burning sensation and recurrent blistering over the sun - exposed areas, which healed with scarring and disfigurement of nails since 1 - year of age", "obvious hypertrichosis over face involving the cheek and forehead, the forearms and multiple bullae over the dorsum of hands, fingers, forearms, and feet with postinflammatory hyperpigmentation and scars over affected skin", "Nails were discolored", "hypertrichosis" ]

[ "birth and mental developmental history were normal" ]

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[ "13 - year - old" ]

[ "since 6 months of age" ]

[ "Based on the clinical presentation with onset in early childhood of a photosensitive disorder with erythrodontia , hypertrichosis , fluorescent red urine , absence of porphobilinogen in urine , and a demonstrated mutation of the UROS gene the child was diagnosed as a case of CEP ." ]

[ "He has now been taken up for bone marrow transplantation with his sister serving as human leukocyte antigens ( HLA ) matched donor ." ]

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[ "suspected acute cholecystitis", "acute cholecystitis", "abdominal pain, nausea, and vomiting", "bout of severe abdominal pain ( diagnosed as cholecystitis )", "contracted gallbladder and stones" ]

[ "We present a case of a 26 - year - old female with suspected acute cholecystitis, mental status changes, and seizures" ]

[ "mental status changes, and seizures", "repeated seizures", "delirium, lower limb weakness, hyporeflexia, and psychological abnormalities", "unexplained behavioral disturbances and lower limb weakness", "cerebrospinal fluid ( CSF ) analysis findings were all within normal range" ]

[ "elevated urinary porphobilinogen, 5 - aminolevulinic acid, and total porphyrins", "DNA molecular testing showed a novel heterozygous mutation ( c. 760delC p. L254X ) in the exon11 of the HMBS gene", "sodium levels ranged between 118–125 mmol / L ( 135–144 mmol / L ), mildly elevated transaminases ( aspartate aminotransferase / alanine transaminase ), and slight elevation of anti - neutrophil antibodies of the perinuclear type ( P - ANCA ). Alkaline phosphatase, bilirubin, complete blood count ( CBC ), thyroid - stimulating hormone ( TSH ), vitamin B12 level – markers for connective tissue diseases, viral titer values, and cerebrospinal fluid ( CSF ) analysis findings were all within normal range", "The abdominal imaging result was normal, except for contracted gallbladder and stones", "Total porphyrins in urine were elevated : 29,100 nmol/24 hours ( normal : ≤214 ), with main elevation in uroporphyrin level, 24,200 nmol/24 hours ( normal : ≤30 ), and mild elevation in coproporphyrin level, 118 nmol/24 hours ( normal : ≤38 ). DNA molecular testing showed a novel heterozygous mutation in the exon 11 of the HMBS gene ( c. 760delC p. L254X" ]

[ "elevated and uncontrolled blood pressure, sinus tachycardia" ]

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[ "abdominal pain, nausea, and vomiting during first pregnancy", "patient delivered a healthy child" ]

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[ "26 - year - old" ]

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[ "AIP" ]

[ "The patient was treated with intravenous heme arginate ( 4 mg / kg / day ) for 5 days , that was followed by an improvement in the chemical and clinical parameters" ]

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[ "A 4 - year - old female patient with a nasal anomaly was admitted to our outpatient clinic" ]

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[ "low levels of androstenedione", "Paranasal sinus computed tomography study revealed that her left - sided accessory nostril opened to the left nasal cavity" ]

[ "patent foramen ovale" ]

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[ "cliteromegaly" ]

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[ "left - sided supernumerary nostril", "Paranasal sinus computed tomography study revealed that her left - sided accessory nostril opened to the left nasal cavity" ]

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[ "She was born 2300 g prematurely on her 37 th gestational week from a 34 - year - old mother with a history of five pregnancies, two still births and two abortions" ]

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[ "4 - year - old" ]

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[ "congenital adrenal hyperplasia" ]

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[ "white blood cell ( WBC ) count was normal" ]

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[ "A 3 - year - old boy was admitted to our emergency department because of convulsions and unconsciousness" ]

[ "convulsions and unconsciousness", "coma and had seizures", "Electroencephalography showed focal epileptic activity", "T2 - weighted and fluid attenuated inversion recovery ( FLAIR ) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical - subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical - subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient ( ADC ) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto - occiptal cortical - subcortical regions due to hypoxia and hypoglisemia", "DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes. The patient exhibited epilepsy as neurological sequelae" ]

[ "Laboratory tests were normal except for hypoglycemia. His plasma glucose level was 20 mg / dl and white blood cell ( WBC ) count was normal. No evidence of serum electrolyte abnormalities was detected. Specific infectious agents were not identified by comprehensive studies", "T2 - weighted and fluid attenuated inversion recovery ( FLAIR ) images revealed increased signal intensities in the bilateral frontal and parietooccippital cortical - subcortical regions and a hyperintense lesion in the splenium of the corpus callosum. Effacement of sulcal spaces was detected compatible with cerebral edema. Hyperintense cortical - subcortical signals and the lesion in the corpus callosum were hyperintense on DWI with reduced apparent diffusion coefficient ( ADC ) maps. There were no signal changes suggesting microhemorrhages on SWI. MRI findings were consistent with cytotoxic cerebral edema in bilateral frontal and parieto - occiptal cortical - subcortical regions due to hypoxia and hypoglisemia", "DWI and FLAIR images on day 20 indicated partial resolution of the high intensity lesions. Hyperintense signal changes gradually decreased and completely disappeared in frontal lobes. However, ventricular dilatation, mild cerebral cortical atrophy, T2 and FLAIR hyperintense signal changes in bilateral occipital lobes were detected on the last MRI. SWI was normal, and DWI showed restricted diffusion in bilateral occipital lobes" ]

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[ "3 - year - old" ]

[ "birth" ]

[ "He had been diagnosed as 21 - hydroxylase deficiency at birth ." ]

[ "He had been taking oral steroid ( hydrocortisone ) replacement therapy since then ." ]

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[ "A 36 years man presented with severe obstructive LUTS" ]

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[ "Prostate specific antigen ( PSA ) was 0.393 ng / mL", "X - ray of pelvis showed punctate calcification in the region of pubic symphysis ( Fig. 1 ), computerized tomography scan of pelvis showed extensive and well calcified areas into the prostatic parenchyma", "Biochemical analysis of urine showed the presence of homogentisic acid", "On biochemical analysis, calculi were composed of calcium oxalate and uric acid", "Punctate calcification in the region of pubic symphysis by X - ray of pelvis", "Extensive prostatic calcification by computerized tomography" ]

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[ "severe obstructive LUTS", "prostate was hard and nodular", "Flow was a Q max of 2 mL / s for a voided volume of 130 mL and post void residual urine volume of 380 mL.", "Prostate specific antigen ( PSA ) was 0.393 ng / mL", "- ray of pelvis showed punctate calcification in the region of pubic symphysis ( Fig. 1 ), computerized tomography scan of pelvis showed extensive and well calcified areas into the prostatic parenchyma", "passage of dark colored urine", "multiple blackish calculi in prostatic urethra and in prostatic fossa", "calculi were composed of calcium oxalate and uric acid", "Punctate calcification in the region of pubic symphysis by X - ray of pelvis", "Extensive prostatic calcification by computerized tomography" ]

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[ "chronic low back ache. He was short statured with kyphotic spine" ]

[ "Osler 's sign ( bluish discolouration of sclera ) was present", "Osler 's sign" ]

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[ "36 years" ]

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[ "These findings confirmed the diagnosis of alkaptonuria ." ]

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[ "short stature ( 145 cm" ]

[ "mild hepatomegaly", "mild hepatosplenomegaly" ]

[ "A 29 - year - old male patient presented with a 6 - year history of asymptomatic progressive cutaneous sclerosis, hyperpigmentation, and hypertrichosis over both thighs and trunk", "diagnosed as Type 1 diabetic 6 years back and was receiving insulin since then" ]

[ "nerve conduction studies were normal" ]

[ "Skin biopsy revealed marked fibrosis of the dermis and subcutaneous tissue. Dermal appendages pushed upward, and a perivascular infiltrate of lymphocytes and histiocytes with foamy cytoplasm were seen intermingled with the bundles of dermal collagen. Septal panniculitis with plasma cell infiltration was noted. Histopathology report suggested sclerodermatous changes with immunostain CD68+ve histiocytes", "Routine laboratory investigations revealed a fasting blood glucose level of 250 mg / dL and random blood sugar of 338 mg / dL with glycated hemoglobin 10.2 %. Thyroid profile, liver function, kidney function, serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal. Antinuclear antibody was negative", "Ultrasound abdomen revealed mild hepatosplenomegaly and abdominal lymphadenopathy. Color Doppler study of the scrotal region revealed small penis, normal echotexture, no calcific plaques, and small left testis. Chest radiography and nerve conduction studies were normal", "Computed tomography ( CT ) demonstrated marked symmetrical thickening of the skin with infiltration of subcutaneous tissue at the lower half of the body from infraumbilical region till scrotum and into bilateral gluteal region down to the knees. Para - aortic and inguinal lymphadenopathy and mild pericardial effusion were noted. Marked thickening of the scrotum was seen" ]

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[ "as Type 1 diabetic", "Axillary and pubic hairs were scanty. Other secondary sexual characters such as facial hair were sparse and voice was normal", "fasting blood glucose level of 250 mg / dL and random blood sugar of 338 mg / dL with glycated hemoglobin 10.2 %", "serum testosterone, follicle stimulating hormone and luteinizing hormone levels were normal" ]

[ "hypospadias, micropenis, scrotal swelling", "small penis, normal echotexture, no calcific plaques, and small left testis", "Marked thickening of the scrotum was seen" ]

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[ "short stature" ]

[ "voice was normal", "Ophthalmologic and auditory examinations were normal" ]

[ "asymptomatic progressive cutaneous sclerosis, hyperpigmentation, and hypertrichosis over both thighs and trunk. He complained of skin tightness around the abdomen while walking", "large ill - defined hyperpigmented indurated plaques extending symmetrically from mid - truncal area to both thighs characteristically sparing the knees and medial aspect of buttocks. A prominent constriction band was noted around the abdomen. The lesions over thighs were associated with hypertrichosis and were warm to touch", "Axillary and pubic hairs were scanty. Other secondary sexual characters such as facial hair were sparse", "Nails and teeth were normal", "Skin biopsy revealed marked fibrosis of the dermis and subcutaneous tissue. Dermal appendages pushed upward, and a perivascular infiltrate of lymphocytes and histiocytes with foamy cytoplasm were seen intermingled with the bundles of dermal collagen. Septal panniculitis with plasma cell infiltration was noted. Histopathology report suggested sclerodermatous changes with immunostain CD68+ve histiocytes", "marked symmetrical thickening of the skin with infiltration of subcutaneous tissue at the lower half of the body from infraumbilical region till scrotum and into bilateral gluteal region down to the knees" ]

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[ "A 29 - year - old" ]

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[ "H syndrome" ]

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[ "chronic diarrhea, and intellectual disability, were not found" ]

[ "A 63 - year - old man presenting with prominent Achilles tendon thickness and plantar xanthomas ( Fig. 1A - C ) was referred to our hospital due to an abdominal pulsatile mass", "He had a history of hypertension for 5 years and a smoking habit ( 10 cigarettes / day", "He was born to consanguineous parents ( second cousins ). He had no familial history of high LDL cholesterol, tendon xanthomas, or premature atherosclerosis" ]

[ "did not show any neuropathyintellectual disability, were not found" ]

[ "Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm", "Coronary angiography revealed mild to moderate coronary atherosclerotic lesions", "modestly elevated LDL cholesterol level ( 166 mg / dL )", "homozygous mutations in the cytochrome P450 subfamily 27 A1 ( CYP27A1 ) gene ( c.410G > A or p. Arg137Gln, Fig. 2A ). This mutation was confirmed by Sanger sequencing", "increased serum level of cholestanol was found ( 5.2 μg / mL, reference range 1.62 - 3.08", "T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) magnetic resonance imaging showed periventricular white matter" ]

[ "abdominal pulsatile mass. Computed tomography revealed the existence of a saccular type AAA, the diameter of which was 52 mm", "history of hypertension for 5 years", "Coronary angiography revealed mild to moderate coronary atherosclerotic lesions", "AAA" ]

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[ "prominent Achilles tendon thickness" ]

[ "juvenile cataract, chronic diarrhea, and intellectual disability, were not found" ]

[ "plantar xanthomas" ]

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[ "63 - year - old" ]

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[ "CTX" ]

[ "Atorvastatin" ]

[ "118 cm tall" ]

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[ "The case was a 65 - year - old female with VDRR who reported progressive weakness of the upper extremities, difficulty walking, neck pain, and numbness in the left arm", "previously undergone T7 – T9 laminectomy due to thoracic myelopathy at another hospital at the age of 24", "At the age of 34, she underwent a second posterior decompression surgery ( T4 – T9 )" ]

[ "progressive weakness of the upper extremities, difficulty walking, neck pain, and numbness in the left arm", "cord compression with ectopic ossification at the rim of the occipital bone and OPLL at C1 level", "difficulty in walking", "gait disturbance due to thoracic myelopathy", "weakness of the upper extremities, difficulty walking, neck pain, and numbness in the left arm", "was able to walk only short distances supporting herself on a wall", "decreased light touch and pinprick sensation, and motor weakness ( 3/5 strength ) in the distal upper extremities. The grip power was 6 kg in both hands. Tendon reflexes were equivocal with indifferent Babinski sign bilaterally", "spinal cord compression at the levels of both the occipital bone and C1", "free of pain and numbness. Her grip power had improved to 20 kg in the right and 15 kg in the left hand. She had regained the ability to walk with the support of a cane" ]

[ "Imaging studies demonstrated cord compression with ectopic ossification at the rim of the occipital bone and OPLL at C1 level. Ankylosis of the whole spine below the C2 vertebra was also noted with preserved mobility only at the craniovertebral junction", "Plain radiograph showed marked kyphosis of the thoracic spine ( T1 – T12 angle; 94 ° ) ( Fig. 1 ). Computed tomography demonstrated ankylosis of the whole spine below the C2 vertebra with extensive ossification of the paraspinal ligaments ( Fig. 2 A, B ). In contrast, decreased but preserved mobility ( 9 ° on flexion and extension ) was noted at the craniovertebral junction ( CVJ ). No overt radiographic instability was found in the atlantoaxial region, with an atlantodental interval of 1 mm. In addition, there was ossification at the rim of the occipital bone, and OPLL at the C1 level. Magnetic resonance imaging ( MRI ) revealed spinal cord compression at the levels of both the occipital bone and C1" ]

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[ "difficulty walking, neck pain", "cord compression with ectopic ossification at the rim of the occipital bone and OPLL at C1 level. Ankylosis of the whole spine below the C2 vertebra was also noted with preserved mobility only at the craniovertebral junction", "difficulty in walking", "gait disturbance due to thoracic myelopathy", "difficulty walking, neck pain", "marked round back and bowed legs", "kyphosis of the thoracic spine ( T1 – T12 angle; 94 °", "ankylosis of the whole spine below the C2 vertebra with extensive ossification of the paraspinal ligaments ( Fig. 2 A, B ). In contrast, decreased but preserved mobility ( 9 ° on flexion and extension ) was noted at the craniovertebral junction ( CVJ ). No overt radiographic instability was found in the atlantoaxial region, with an atlantodental interval of 1 mm. In addition, there was ossification at the rim of the occipital bone, and OPLL at the C1 level" ]

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[ "65 - year - old" ]

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[ "VDRR", "diagnosed with VDDR" ]

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[ "A 9 - year - old boy, diagnosed with CAH at the age of 1 year following an adrenal crisis, was poorly controlled due to lack of compliance. He presented with precocious puberty, short stature, and aggressive behaviour" ]

[ "aggressive behaviour" ]

[ "On ultrasound, there were well - defined, heterogeneous, predominantly hypoechoic, round - to - oval masses in both testes", "The cortisol level was low, and levels of 17 alpha - hydroxyprogesterone, plasma corticotrophin ( ACTH ), and testosterone were high", "Scrotal ultrasound revealed well - defined, heterogeneous, predominantly hypoechoic, round - to - oval masses with posterior acoustic shadowing in both testes, in the medial aspects near the mediastinum testis. The right testicular mass measured 1.3×1.1 cm, and the left testicular mass measured 1.5×1.2 cm ( Figures 1, 2 ). On colour Doppler, the masses had minimal internal vascularity ( Figure 3 ). The rest of the testes showed normal flow. The epididymis and cord structures were normal. There was no evidence of hydrocoele on both sides. Testicular tumor markers were negative. Abdominal ultrasound did not reveal any mass lesion in the suprarenal region, ruling out adrenal gland enlargement", "decrease in testosterone and 17 alpha - hydroxyprogesterone levels; however, the testicular masses did not significantly change in size on follow up ultrasound performed after 3 and 6 months" ]

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[ "precocious puberty", "testicular adrenal rest tumor", "adrenal crisis", "precocious puberty, short stature", "The cortisol level was low, and levels of 17 alpha - hydroxyprogesterone, plasma corticotrophin ( ACTH ), and testosterone were high", "Abdominal ultrasound did not reveal any mass lesion in the suprarenal region, ruling out adrenal gland enlargement", "bilateral testicular masses that had a typical sonographic appearance", "testicular adrenal rest tumor", "decrease in testosterone and 17 alpha - hydroxyprogesterone levels; however, the testicular masses did not significantly change in size on follow up ultrasound performed after 3 and 6 months" ]

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[ "short stature" ]

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[ "9 - year - old", "A 9 - year - old" ]

[ "age of 1 year" ]

[ "diagnosis of CAH and precocious puberty", "Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses , a diagnosis of testicular adrenal rest tumor was made", "diagnosed with CAH at the age of 1 year following an adrenal crisis", "In a patient with CAH and bilateral testicular masses that had a typical sonographic appearance , a diagnosis of testicular adrenal rest tumor was made" ]

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[ "Complete blood count and liver function tests were also normal", "the patient ’s SpO 2 remained between 97 % and 100", "heart rate varied from 82 to 96 beat / min", "Vital signs were stable during the surgery" ]

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[ "A 19 - year - old female was presented with palmoplantar hyperkeratosis from the age of 4 years and complete loss of teeth by the age of 14 which was the characteristic criteria for PLS. She was the second child born to apparently healthy consanguineous parents ( cousins ). Her older brother also suffered from PLS but two younger siblings were normal. Previous medical history showed that her permanent and deciduous teeth were lost after erupting normally", "We report a 19 - year - old girl with palmoplantar hyperkeratosis who presented total loss of her teeth" ]

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[ "In the panoramic view, severe maxillary and mandibular bone resorption along with bilateral pneumatization of maxillary sinuses were seen. Her chin was small but the other systemic examinations, routine laboratory examinations, chest X - ray, and skull X - ray were normal", "Complete blood count and liver function tests were also normal" ]

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[ "complete loss of teeth by the age of 14 which", "permanent and deciduous teeth were lost after erupting normally", "complete edentulous ridges with normal overlying mucosa", "total loss of her teeth" ]

[ "palmoplantar hyperkeratosis from the age of 4 years", "diffuse palmoplantar keratoderma", "palmoplantar hyperkeratosis" ]

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[ "19 - year - old", "19 - year - old" ]

[ "age of 4 years" ]

[ "characteristic criteria for PLS" ]

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[ "he weighed 38 kg and his height was 148 cm", "pulse rate was 47 / minute" ]

[ "recurrent episodes of vomiting", "liver was not enlarged" ]

[ "A 14 - year - old boy was referred to our unit with a clinical diagnosis of Kearns Sayre Syndrome. He had presented with progressive ptosis over a period of 18 months and decreased vision in dim light", "His parents reported that he was not a sporty person and became fatigued earlier than his peers during physical activities" ]

[ "no episodes of syncope, pre - syncope or night terrors", "His developmental history was normal", "Clinical evaluation of the neurological system was normal" ]

[ "Investigations had shown a mild elevation of lactates but tandem mass spectrometry was non - diagnostic", "His chest x - ray showed a normal cardiac silhouette with clear lung fields. Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits", "Genetic testing revealed a large mitochondrial DNA deletion that on mapping proved to be a novel mutation not previously reported in literature ( a 3898bp deletion m.6162_10059del that does not occur at a repeat sequence" ]

[ "low heart rate", "not associated with breathlessness or chest pain. There were no episodes of syncope, pre - syncope", "peripheral perfusion was good and all peripheral pulses were felt equally", "regular pulses and a normal volume", "no clinical evidence of cardiomegaly. His first heart sound was normal, second heart sound was normally split and a grade 2/6 ejection systolic murmur was heard in the left 2nd intercostal space", "His chest x - ray showed a normal cardiac silhouette", "Echocardiogram conformed a structurally normal heart. The left ventricular dimensions and systolic function were within normal limits", "His electrocardiogram revealed complete atrio - ventricular disassociation with an atrial rate of 100 / min and a broad complex ventricular escape rhythm with a rate of 43 / minute ( Fig. 2 ). The QRS duration was 160 milliseconds. The QT interval was 520 milliseconds and the QTc was calculated to be 474 milliseconds", "Electrocardiogram showing evidence of complete heart block with an atrial rate of 100 / minute and a broad complex escape rhythm with a ventricular rate of 43 / minute", "improvement in his effort levels as well as appetite", "his parents returned home at 12.30 PM to find him sitting on the sofa with his earphones over his ears and his computer by his side apparently asleep. He had contacted his mother approximately 45 minutes earlier. They found him to be unresponsive" ]

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[ "not associated with breathlessness or chest pain", "His chest was clear on auscultation", "clear lung fields" ]

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[ "progressive ptosis over a period of 18 months and decreased vision in dim light. His ophthalmic evaluation had confirmed external ophthalmoplegia and a pigmentary degeneration of his retina", "Fundoscopic picture showing evidence of pigmentary degeneration of the peripheral retina" ]

[ "no dysmorphic features or congenital anomalies" ]

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[ "14 - year - old" ]

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[ "Kearns Sayre Syndrome" ]

[ "As KSS is associated with progressive conduction system disease and his escape rhythm appeared to be of infra - Hisian rhythm he was implanted with a dual chamber transvenous pacing system ( St Jude 's Accent MRI system with 52 cm ( atrial ) and 58 cm ( ventricular ) St Jude Tendril MRI leads ) . The pacemaker was set in DDD mode with a lower rate of 50 / min , a maximum sensor rate of 110 / minute and an upper tracking rate of 130 / minute ." ]

[ "pulmonary embolism" ]

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[ "A known case of hypertension, asthma and AKU presented to Urology clinic complaining of severe LUTS : obstructive symptoms including poor stream, straining, hesitancy, and incomplete emptying of urinary bladder, in addition to irritative symptoms including frequency, urgency and nocturia. These symptoms started 2 months prior to his current presentation with a history of passing stones during urination and acute urinary retention that was relieved by suprapubic catheterization and cystolitholapaxy for his urinary bladder stones. He also reports blackish discoloration of his urine and history of recurrent urinary tract infections ( UTIs" ]

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[ "Supine KUB ( A ) showing numerous radiopaque stones at the projection of urinary bladder and prostate, note also advanced changes of alkaptonuria seen in spine, pre - operation non - contrast urinary tract CT ( B + C ) showing multiple stones in the urinary bladder and prostate", "Laboratory investigations revealed a normal complete blood count, kidney function tests, serum parathyroid hormone, uric acid, calcium, and prostate specific antigen ( PSA ). The only positive finding was the presence of red blood cells and white blood cells in his urine analysis; however, his urine culture results came back negative", "Post operation non - contrast urinary tract CT ( A + B ) showing only few residual stones, the largest on the right side of the prostate and pelvic MRI coronal STIR ( C ) showing fluid filled diverticulum in the left lateral aspect of the prostate ( arrow ), axial T2 ( D ) showing the prostatic diverticulum containing tiny hypointense stone", "Axial non - contrast urinary tract CT ( A + B ) show near completely removal of all stones ( residual tiny stone in the prostate", "chemical calculus analysis showed black stones with a composition of 20 % uric acids and 80 % calcium oxalate" ]

[ "hypertension", "pulmonary embolism" ]

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[ "severe LUTS : obstructive symptoms including poor stream, straining, hesitancy, and incomplete emptying of urinary bladder, in addition to irritative symptoms including frequency, urgency and nocturia. These symptoms started 2 months prior to his current presentation with a history of passing stones during urination and acute urinary retention", "blackish discoloration of his urine and history of recurrent urinary tract infections ( UTIs", "urethral stone was felt in the shaft of the penis during palpation, bladder was not full", "prostate was hard with indentation mostly representing palpable stones in the prostatic urethra and para prostatic diverticulum", "Supine KUB ( A ) showing numerous radiopaque stones at the projection of urinary bladder and prostate", "pre - operation non - contrast urinary tract CT ( B + C ) showing multiple stones in the urinary bladder and prostate", "presence of red blood cells and white blood cells in his urine analysis; however, his urine culture results came back negative", "Post operation non - contrast urinary tract CT ( A + B ) showing only few residual stones, the largest on the right side of the prostate", "pelvic MRI coronal STIR ( C ) showing fluid filled diverticulum in the left lateral aspect of the prostate ( arrow ), axial T2 ( D ) showing the prostatic diverticulum containing tiny hypointense stone", "complicated by clot retention", "urethral and left paraprostatic diverticulum with multiple black stones", "residual tiny stone in the prostate", "weight of the stones was 78 g, and chemical calculus analysis showed black stones with a composition of 20 % uric acids and 80 % calcium oxalate", "was passing urine with good stream", "without any bothersome urinary symptoms" ]

[ "asthma", "pulmonary embolism" ]

[ "presence of thoracic lumbar back pain for the past 3 years with an incidental finding of advanced changes of AKU seen in the spine ( Fig. 1 A. KUB ), short stature", "advanced changes of alkaptonuria seen in spine" ]

[ "black discoloration of the nose and ear cartilages" ]

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[ "AKU", "alkaptonuria" ]

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[ "The blood pressure at clinic was 80/50 mm Hg", "104.5 cm tall and weighs 23.3 kg" ]

[ "vomiting", "vomiting" ]

[ "An 11 - month - old baby girl presented to the outpatient clinic at Peking Union Medical College Hospital with skin hyperpigmentation and vomiting for 2 weeks. The child was born at full - term by Cesarean section and was the second child of the nonconsanguineous parents. The patient 's older sibling was phenotypically female, but died in infancy without a clear diagnosis", "Both parents were found to be heterozygous for the variant", "patient 's paternal grandfather and maternal grandmother both carried the same mutant allele; her paternal grandmother and maternal grandfather were negative for the mutant allele. All the family members denied consanguinity and no subclinical phenotypes ( such as mild amenorrhea in women ) were recorded, and there were no abnormalities in physical and laboratory examinations", "A case was reported that an 11 - month - old Chinese girl who presented with a sex development disorder and hyponatremia" ]

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[ "hyponatremia and an elevated adrenocorticotropic hormone ( ACTH ) level were detected by tests.", "the baby had a mildly elevated cholesterol level of 5.72 mmol / L ( normal : 2.85–5.70 mmol / L ), but a normal triglyceride level. Her plasma sodium level was 131.7 mmol / L ( normal : 135–145 mmol / L ) with potassium concentration of 6.61 mmol / L ( normal : 3.5–5.5 mmol / L ). ACTH was > 1250 pg / mL ( 0–46 pg / mL ) with a morning cortisol of 1.23 μg / dL ( normal : 4–22 μg / dL ). Baseline sex hormone tests revealed luteinizing hormone < 0.10 U / L, follicle stimulating hormone 1.78 U / L, testosterone 2.50 ng / dL, progesterone 0.44 ng / dL, estradiol 22.99 pg / mL, and dehydroepiandrosterone ( DHEA ) sulfate < 0.1 μg / dL. Adrenal computed tomography ( CT ) scan revealed enlarged adrenal glands. Neither ovaries nor uterus could be identified with pelvic ultrasound. However, testicular - like tissues were detected in the bilateral inguinal regions ( left : 0.6 × 0.4 cm; right : 0.7 × 0.4 cm ) by ultrasonography. Plasma renin activity ( PRA ) was 0.11 ng / mL per h ( normal : 0.93–6.56 ng / mL per h ) with a normal aldosterone level of 8.84 ng / dL ( normal : 6.5–29.6 ng / dL ).", "a homozygous variant c.707_708delins CTT ( p. Lys236Thrfs∗47 ) was found on exon 6 of the STAR gene.", "Both parents were found to be heterozygous for the variant ( c.707_708delins CTT, p. Lys236Thrfs∗47 ) at the same locus of the STAR gene without phenotypic consequences.", "The patient 's paternal grandfather and maternal grandmother both carried the same mutant allele", "hyponatremia", "The girl presented with hyponatremia, decreased cortisol level, elevated adrenocorticotropic hormone level and female vulva despite a 46, XY karyotype. Enlarged adrenal glands and testicular - like tissue in the bilateral inguinal regions were detected with abdominal ultrasound." ]

[ "Lacking hypertension" ]

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[ "female external genitalia", "plasma sodium level was 131.7 mmol / L ( normal : 135–145 mmol / L ) with potassium concentration of 6.61 mmol / L ( normal : 3.5–5.5 mmol / L )", "Neither ovaries nor uterus could be identified with pelvic ultrasound. However, testicular - like tissues were detected in the bilateral inguinal regions ( left : 0.6 × 0.4 cm; right : 0.7 × 0.4 cm ) by ultrasonography", "ambiguous genitalia", "sex development disorder", "hyponatremia", "hyponatremia", "female vulva despite a 46, XY karyotype", "testicular - like tissue in the bilateral inguinal regions" ]

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[ "skin hyperpigmentation", "skin hyperpigmentation" ]

[ "was born at full - term by Cesarean section" ]

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[ "11 - month - old", "11 - month - old" ]

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[ "She was suspected of having LCAH , and definitive diagnosis was made after Sanger sequencing detected a homozygous frameshift variant c.707_708delins CTT ( p. Lys236Thrfs∗47 ) on exon 6 of the STAR gene ." ]

[ "The patient was prescribed hydrocortisone 10 to 12 mg / m 2 and 9α - fludrocortisone 100 μg / d." ]

[ "normal vital signs" ]

[ "neuro - visceral and psychiatric manifestations", "right lower abdominal pain and distension for 2 weeks. The pain was colicky, episodic, with no precipitating factors and only relieved after bowel motion", "mild pain distress", "acute abdominal pain", "abdominal pain", "four recurrent milder attacks in the form of abdominal and back pain" ]

[ "We present a 24 year - old woman who developed acute intermittent porphyria five days after right hemi - colectomy", "A 24 year - old- single female patient was admitted because of right lower abdominal pain and distension for 2 weeks. The pain was colicky, episodic, with no precipitating factors and only relieved after bowel motion. She had no constitutional symptoms of chronic illness. She was not on any medications and her social history was unremarkable. Her menstrual cycle was regular and she was menstruating one day after admission", "the family history showed that two of her cousins ( from mother side ) had AIP" ]

[ "neuro - visceral and psychiatric manifestations", "sudden deterioration of consciousness level and became unresponsive with a Glasgow Coma Scale of 7/15. Her pupils were dilated and had a sluggish reaction to light", "brain CT scan and magnetic resonance imaging ( MRI ), and cerebrospinal fluid analysis. These tests and septic work - up were normal", "developed altered mental status, personality changes, visual and auditory hallucinations with euphoric and aggression episodes", "neurological and psychiatric symptoms", "four recurrent milder attacks in the form of abdominal and back pain and confusion" ]

[ "positive urine test for porphobilinogen", "presence of a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene ( c.760delC p Leu254 )", "Routine laboratory tests including CBC and renal and liver function tests were normal. Serum transaminases remained normal during her hospital stay. Aspartate aminotransferase ( AST, SGOT ) range was 18–33 U / L ( normal range : 15–37 U / L ). Alanine aminotransferase ( ALT, SGPT ) range was 25–51 U / L ( normal range : 14–63 U / L ). On admission, level of serum sodium ( Na ) was normal : 138 mEq / L ( normal range 135–145 mEq / L ) and remained normal ( range : 135–139 mEq / L ) until the 5th postoperative day", "Plain abdominal X - ray and abdominal computed tomography ( CT ) showed a distended cecum located in the pelvis with fecal impaction; the rest of the viscera were unremarkable", "The histology revealed normal colon", "Blood work up revealed severe hyponatremia; serum Na : 107 mEq / l with normal renal and liver function tests", "brain CT scan and magnetic resonance imaging ( MRI ), and cerebrospinal fluid analysis. These tests and septic work - up were normal", "presence of high PBG in the urine", "she was found to have a heterozygous mutation in the hydroxyrmethylbilane synthase ( HMBS ) gene ( c.760delC p Leu254" ]

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[ ". Her menstrual cycle was regular and she was menstruating one day after admission." ]

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[ "a 24 year - old", "24 year - old-" ]

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[ "acute intermittent porphyria", "The diagnosis of AIP was based on the presence of high PBG in the urine ( test was done at another center ) ." ]

[ "high carbohydrate intake .", "regime of IV hematin ( heme arginate ) 4 mg / Kg body weight / day for three days .", "prophylactic IV hematin 4 mg / Kg body weight / day for three days" ]

[ "polycythemia ( hemoglobin : 18.0 g / dL; red blood count : 627 × 10 4; hematocrit : 53.1 %", "height : 165 cm; weight : 79 kg; Body Mass Index : 29.0 kg / m²", "polycythemia also improved to a Hb level of 15.2 g / dL.", "height : 1.58 m; weight : 65 kg; body mass index : 23.9 kg / m²" ]

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[ "A 41 year old man was followed at the local clinic for polycythemia ( hemoglobin : 18.0 g / dL; red blood count : 627 × 10 4; hematocrit : 53.1 % ) and hypertension", "A 41 year old man was referred to Kobe City Medical Center West Hospital, Kobe City, Japan, because of 2 years of infertility", "female offspring ( 3650 g ) who was confirmed as negative for CAH by serum 17‐OHP and 21‐deoxycortisol measurement." ]

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[ "polycythemia ( hemoglobin : 18.0 g / dL; red blood count : 627 × 10 4; hematocrit : 53.1 % )", "An abdominal CT scan for the examination of these conditions revealed the enlargement of the bilateral adrenal glands", "The laboratory tests revealed an extremely high level of ACTH ( 316.4 pg / mL ) and a relatively low level of cortisol ( 6.8 μg / dL ). Although the patient did not have any family history of CAH, the CT findings regarding the adrenal glands, unbalanced pituitary – adrenal hormones, and high level of serum 17‐OHP ( 62.7 ng / mL ) indicated the possibility of CAH.", "The abnormality in the pituitary – gonadal hormonal status ( FSH : < 0.1 IU / mL; LH : < 0.1 IU / mL; testosterone : 10.9 ng / mL; estradiol : 29 pg / mL ) indicated the excessive secretion of adrenal androgens. Bilateral testicular tumors were identified in a scrotal ultrasound echo scan", "All the serum markers for testicular tumors were within the normal range and the testicular MRI showed the same sign as case 1 ( Figure 6 A ). The semen analysis showed azoospermia. A genetic diagnosis by PCR‐direct sequencing proved CAH due to 21‐hydroxylase deficiency due to CYP21A2 gene mutation", "A scrotal ultrasound examination confirmed the presence of bilateral heteroechogenic, hypovascularized masses near the testes ( Figure 2 A ). The semen analysis revealed oligoasthenozoospermia ( volume : 2.6 mL; concentration : 7 × 10 6 /mL; motility : 14 % ). The hormonal examination revealed a normal hormonal status of serum follicle‐stimulating hormone ( FSH ) of 2.7 mIU / mL, luteinizing hormone ( LH ) of 1.3 mIU / mL, testosterone of 4.3 ng / mL, and estradiol of 13 pg / mL. All the serum markers for testicular tumors, including human chorionic gonadotropin, alpha‐fetoprotein, and lactate dehydrogenase, were within the normal range. The pelvic magnetic resonance imaging ( MRI ) scan showed irregular, margin, heterogeneous low‐signal‐intensity tumors that were surrounded by high‐signal normal testicular tissue in the T2‐weighted image ( Figure 3 ). An enhanced computed tomography ( CT ) scan revealed diffuse, irregular enlargement of both adrenal glands, with no finding in the testes ( Figure 4 A, B ). Bilateral testicular atrophy and bilateral enlargement of the adrenal glands without any other metastases did not seem to be typical for malignant testicular tumors.", "In the endocrinological examination, both the serum ACTH and 17‐OHP levels were extremely high ( 69.3 pg / mL and 112 ng / mL, respectively ). Genetic diagnosis by polymerase chain reaction ( PCR)‐direct sequencing confirmed the 21‐hydroxylase deficiency due to CYP21A2 gene mutation ( I‐172N mutation" ]

[ "hypertension" ]

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[ "Bilateral testicular tumors were identified in a scrotal ultrasound echo scan", "both testes had become slightly atrophied ( right : 14 mL; left : 12 mL ) ( performed with a Prader orchidmeter ) and no induration was palpated", "serum markers for testicular tumors were within the normal range and the testicular MRI showed the same sign as case 1 ( Figure 6 A ). The semen analysis showed azoospermia", "Sperm emerged ( concentration : 3.4 × 10 6 /mL; motility : 26 % )", "size reduction in the adrenal hyperplasia and TART", "infertility", "Both testes had become atrophied ( 9 mL ) ( performed with a Prader orchidmeter ) and pea‐sized indurations were felt around the epididymal head in both testes. A scrotal ultrasound examination confirmed the presence of bilateral heteroechogenic, hypovascularized masses near the testes ( Figure 2 A ). The semen analysis revealed oligoasthenozoospermia ( volume : 2.6 mL; concentration : 7 × 10 6 /mL; motility : 14 % )", "irregular, margin, heterogeneous low‐signal‐intensity tumors that were surrounded by high‐signal normal testicular tissue in the T2‐weighted image", "no finding in the testes", "Bilateral testicular atrophy", "semen analysis revealed a significant change ( concentration : 34 × 10 6 /mL; motility : 59 % ), along with normalization of the testicular size ( right : 14 mL; left : 16 mL ). The size reduction of the TART was identified by ultrasound" ]

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[ "41 year old" ]

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[ "Testicular adrenal rest tumor ( TART ) is one of the possible causes of male infertility , accompanied by congenital adrenal hyperplasia ( CAH )" ]

[ "After 6 months of low‐dose , daily oral glucocorticoid therapy ( 0.5 mg / d ) , the serum FSH , LH , testosterone , and estradiol levels returned to normal levels ( 9.2 IU / mL , 1.8 IU / mL , 0.8 ng / mL , and < 10 pg / mL , respectively ) . The polycythemia also improved to a Hb level of 15.2 g / dL.", "a low‐dose , oral glucocorticoid of 0.5 mg / d was started under the diagnosis of CAH" ]

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[ "In 1989, a 21 - year - old male experienced visual loss after diving from a diving board", "Twenty years later, in April 2009, he presented again because of recent visual loss in the left eye" ]

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[ "Three biopsies from the flexural skin of the axilla and the neck did not reveal PXE related changes", "Analysis showed that our patient was homozygous for the R1141X - mutation in the ABCC6 - gene" ]

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[ "visual loss after diving from a diving board", "bilateral subretinal hemorrhages and angioid streaks. After clearing of the hemorrhages, more breaks of Bruch ’s membrane were identified. The macula was not affected and vision returned to normal in both eyes", "recent visual loss in the left eye", "Visual acuity ( VA ) was 20/25 in the right eye ( RE ) and 20/40 in the left eye ( LE )", "Clinical examination, FA, and OCT revealed active choroidal neovascularisation nasal to the fovea with leakage and edema", "observed in both eyes angioid streaks, peau d’orange and a few comet tails", "sequellae of diving induced breaks of Bruchs ’ membrane with linear vertical break formation, different from the irregular course and spiderweb configuration of the angioid streaks", "growth of the choroidal neovascularization ( CNV ) was observed with further deterioration of vision. In January 2010, active CNV was also identified in the right eye", "VA was 20/60 in the right eye and 20/250 in the left eye, with in the left eye a large subfoveal CNV expanding on both sides of the fovea, and in the RE a smaller and mildly active subfoveal CNV" ]

[ "no typical plucked - chicken appearance, no papules, macules or other skin lesions. Three biopsies from the flexural skin of the axilla and the neck did not reveal PXE related changes" ]

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[ "21 - year - old" ]

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[ "PXE" ]

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[ "height and weight were 86 cm and 12.5 kg, respectively ( both were below the 3rd percentile, according to China 's 1995 urban 0–18 year - old male height percentiles scale", "height and weight were still below the 3rd percentile, at 116 cm and 20.1 kg, respectively", "his height and weight reached 121 cm and 22 kg" ]

[ "showed a preference for carbohydrate intake from infancy, with a clear aversion to animal proteins and was prone to vomiting", "short stature and excessive thinness" ]

[ "The patient was born at 36 +4 weeks ’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia. His developmental milestones were unremarkable before 1 year of age. Following this, his developmental milestones became delayed, for example, the boy began to walk at 1 year and 6 months and his walk was slower than normal and clumsy. There was no family history of severe childhood illness, death, or stunting. The boy showed a preference for carbohydrate intake from infancy, with a clear aversion to animal proteins and was prone to vomiting. The boy has a sister showing normal development. The boy presented to our child health clinic at age 3 years and 7 months because of his short stature and excessive thinness", "At 10 years old, the boy presented to our pediatric neurological clinic because of a single episode of generalized tonic seizure. The boy had previously had a seizure at 8 years old when receiving tetanus antitoxin treatment after head trauma. During clinic counseling, one of his parents noted that the patient had gait disturbance for almost 1 year, attributed to a persistent tightening of both knee joints. The boy could not jump and easily fell when he ran and walked. The boy, who was in primary school, also showed poor academic performance", "A Chinese boy initially presented with severe stunting and partial growth hormone deficiency ( PGHD ) at 3 years old and was initially treated with growth hormone replacement therapy. Seven years later ( at 10 years old ), he presented with spastic diplegia, cognitive function lesions, epilepsy, and peripheral neuropathy." ]

[ "developmental milestones became delayed", "began to walk at 1 year and 6 months and his walk was slower than normal and clumsy", "A neurologic examination focusing on the motor and sensory nervous system and cerebellar function produced unremarkable findings", "a single episode of generalized tonic seizure", "previously had a seizure at 8 years old when receiving tetanus antitoxin treatment after head trauma", "gait disturbance for almost 1 year, attributed to a persistent tightening of both knee joints. The boy could not jump and easily fell when he ran and walked. The boy, who was in primary school, also showed poor academic performance", "muscle strength of the low extremities was grade 4 ( Oxford Scale ), and he showed increased distal muscle tone than normal, hyper - reflexia, and a negative Babinski sign", "normal, as were the results of cranial MRI and electroencephalography", "peripheral nerve examination revealed reduced compound muscle action potential ( CMAP ) of the right peroneal nerve and bilateral tibial nerve, while the right peroneal nerve distal latency was suspected to be prolonged", "A muscle biopsy revealed neurogenic lesion", "His intelligence quotient was lower than normal, at 80", "mental state and vomiting had clearly improved", "spastic diplegia symptoms had not improved", "spastic diplegia, cognitive function lesions, epilepsy, and peripheral neuropathy" ]

[ "Blood tests showed mildly elevated blood ammonia and creatine kinase, and persistently elevated bilirubin.", "Laboratory tests revealed retardation of bone age ( equivalent to a 1 year old ) and mildly elevated total bilirubin ( 29.4 μmol / L, normal range : 2–24 μmol / L ), direct bilirubin ( 10.4 μmol / L, normal range : 0–7 μmol / L ), and indirect bilirubin levels ( 18.6 μmol / L, normal range : 1.7–17 μmol / L ) but normal hepatic enzyme levels. Blood glucose was slightly lower than normal ( 3.52 mmol / L, normal range : 3.9–6 ), whereas his electrolytes were normal. Screening tests for hepatitis B and A were negative. A growth hormone excitement test revealed low levels of growth hormone ( 0 minute : 0.76 ng / mL; 30 minutes : 4.5 ng / mL; 60 minutes : 6.3 ng / mL; 90 minutes : 4.1 ng / mL; and 120 minutes : 1.5 ng / mL ). An MRI revealed a normal pituitary gland, and thyroid function was normal.", "Laboratory tests revealed mildly elevated hepatic enzyme levels, including aspartate transaminase ( 50.9 IU / L, normal range : 0–50 IU / L ) and alanine transaminase ( 52 IU / L, normal range : 0–45 IU / L ), as well as mildly elevated total bilirubin ( 47.7 μmol / L, normal range : 0–25 μmol / L ), direct bilirubin ( 16.4 μmol / L, normal range : 0–6.8 μmol / L ), and indirect bilirubin levels ( 31.3 μmol / L, normal range : 0–25 μmol / L ). His creatine kinase ( 564.4 IU / L, normal range : 55–190 IU / L ) and blood ammonia levels ( 62.3 mmol / L, normal range : 9–30 mmol / L ) were slightly elevated. A urine occult blood test was positive ( + + ). Red blood cells ( 3–4 / HP, normal range : 0–3 / HP ) were evident in a urine sediment microscopy. Both renal ultrasound and renal function were normal, as were the results of cranial MRI and electroencephalography.", "A muscle biopsy revealed neurogenic lesion ( Fig. 1 ). A gene test was performed and the results demonstrated that he carried compound homozygote mutations of ARG1 ( c.32 T > C )", "Subsequently, his blood and urine amino acid levels were analyzed, revealing a blood arginine concentration of 108.42 μM ( normal range : 10–50 μM ) as well as elevated urinary excretion of orotic acid; however, his blood citrulline, glutamine, glutamate, and alanine concentrations were normal" ]

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[ "retardation of bone age ( equivalent to a 1 year old )", "Blood glucose was slightly lower than normal ( 3.52 mmol / L, normal range : 3.9–6", "A growth hormone excitement test revealed low levels of growth hormone ( 0 minute : 0.76 ng / mL; 30 minutes : 4.5 ng / mL; 60 minutes : 6.3 ng / mL; 90 minutes : 4.1 ng / mL; and 120 minutes : 1.5 ng / mL ). An MRI revealed a normal pituitary gland, and thyroid function was normal", "PGHD", "severe stunting and partial growth hormone deficiency ( PGHD )" ]

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[ "muscle strength of the low extremities was grade 4 ( Oxford Scale )", "His creatine kinase ( 564.4 IU / L, normal range : 55–190 IU / L ) and blood ammonia levels ( 62.3 mmol / L, normal range : 9–30 mmol / L ) were slightly elevated" ]

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[ "born at 36 +4 weeks ’ gestation with a birth weight of 2500 g. Three days after birth, he was hospitalized for several days due to transient hypoglycemia." ]

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[ "10 years old" ]

[ "1 year of age" ]

[ "argininemia with homozygous mutation ( c.32T > C ) of the ARG1 gene", "argininemia" ]

[ "Following the diagnosis , we recommended that the patient begins a low - protein diet ( 0.8 g / kg / day ) to decrease his blood arginine levels , as well as start taking citrulline ( 150–200 mg / kg / day ) ." ]

[ "The patient 's height and body weight were 85.0 cm and 11.6 kg, respectively. Her weight - for - height Z - score ( −0.3 ) was in the 15th–50th percentile of the World Health Organization ( WHO ) growth standards", "Her body weight continuously declined from 11.6 kg to 10.5 kg, and her weight - for - height Z - score ( −1.6 ) decreased to the 3rd–15th percentile of the WHO growth standards" ]

[ "swallowing difficulty", "symptoms of aspiration while swallowing and prolonged feeding time", "irregularly ingested a soft and blended diet", "She had difficulty in eating and she showed signs of aspiration ( e.g., coughing, gagging )" ]

[ "A 22 - month - old girl diagnosed with Sandhoff disease was referred to our hospital with chief complaints of spasticity and swallowing difficulty as well as difficulty with head control" ]

[ "chief complaints of spasticity and swallowing difficulty as well as difficulty with head control.", "She was able to stand while holding on to something at 8 months of age, which suggested normal development. However, developmental arrest occurred at 13 months of age. Spasticity and genu recurvatum were observed while standing and holding on to something. The patient showed a progressive motor regression pattern, and at 18 months of age, she could barely maintain a propped sitting position. At 20 months of age, she showed symptoms of aspiration while swallowing and prolonged feeding time.", "At the time of admission, physical examination revealed grade 3 and 2 muscle strength in the upper and lower extremities, respectively. Neurological examination showed sustained ankle clonus and increased deep tendon reflexes in all extremities as well as hypertonicity and decerebrate posture manifested by an exaggerated extensor posture of all extremities, while crying and/or when she was irritable ( Fig. 2 ). In terms of spasticity, her four extremities scored grade 2 based on the modified Ashworth scale ( MAS ). Overall, the patient had developmental regression. Especially, she showed a delay in development by 1 month in gross - motor domain, by 3 months in language and fine motor domain, and by 2 months in personal - social interaction domain in the Denver Developmental Screening Test II.", "She had difficulty in eating and she showed signs of aspiration ( e.g., coughing, gagging ). Moreover, she had a poor feeding posture with inadequate trunk and head support. Oral motor function assessment showed that the patient had increased tone and decreased movement of the tongue and hypersensitivity in the oral and perioral areas" ]

[ "Brain magnetic resonance imaging scans obtained at 15 months of age did not show delayed myelination or abnormal enhancement", "The patient underwent hexosaminidase assay in white blood cells, which showed increased hexosaminidase A ( % ) and decreased total hexosaminidase. The total hexosaminidase A & B and hexosaminidase A levels were 321.2 nmol / hr / mg ( reference range, 620–1,000 nmol / hr / mg ) and 74.3 % ( reference range, 55%–72 % ), respectively", "videofluoroscopic swallowing study ( VFSS ), and was given barium - containing free water, yogurt ( thick liquid ), and rice porridge ( soft ). In the oral phase, motor control, including lip sealing, tongue control, and mastication, was inadequate with delayed oral transit time ( 1.3 seconds ) and premature bolus loss. In the pharyngeal phase, a delayed swallow reflex was observed without aspiration or penetration during or after swallowing" ]

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[ "symptoms of aspiration while swallowing", "signs of aspiration ( e.g., coughing, gagging )" ]

[ "genu recurvatum" ]

[ "the patient did not show cherry red spot on fundoscopy" ]

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[ "born at full term through normal vaginal delivery" ]

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[ "22 - month - old" ]

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[ "Sandhoff disease", "the patient was diagnosed with Sandhoff disease ." ]

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[ "vital signs on admission showed uncontrolled hypertension ( BP = 148/118 mm Hg ) and tachycardia ( HR = 120 bpm )." ]

[ "history of recurrent abdominal pain", "nausea, vomiting, worsening of abdominal pain, and constipation", "unable to eat", "abdominal pain persisted", "abdominal pain resolved in less than 24 h" ]

[ "This is a 20 - year - old female with a 6 - month history of recurrent abdominal pain. She underwent cholecystectomy 3 months prior to admission but had no relief of her symptoms. She was admitted with acute pyelonephritis, nausea, vomiting, worsening of abdominal pain, and constipation for three days" ]

[ "two generalized tonic – clonic seizures", "she continued to be lethargic, and a stat EEG was requested, that showed LPDs + F over the right temporoparietal region", "She became profoundly lethargic and assumed a fetal position in bed. On neurological examination, there were left lower extremity clonus and a left Babinski sign. Head CT was normal, cerebral spinal fluid ( CSF ) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus. The brain MRI showed PRES", "cEEG was initiated to rule out the possibility of recurrent electrographic seizures or nonconvulsive status epilepticus ( Fig. 2 ). There was one electrographic seizure arising from the right temporoparietal region lasting less than 1 min seen during the first 12 h of recording but none afterwards during the next two days of recording", "neurological exam was normal", "follow - up brain MRI showed remarkable improvement" ]

[ "Head CT was normal, cerebral spinal fluid ( CSF ) was unremarkable, and comprehensive CSF profiles were negative, including PCR for Herpes Simplex virus, Varicella Zoster virus, Lyme disease, and Cryptococcus. The brain MRI showed PRES", "Urine, then serum and fecal porphyrins were requested. The results were as follows : urine PBG level was 177.4 μmol / L ( reference : 0 to 0.88 μmol / L ), serum porphyrin level was 58 nmol / L ( reference : 0 to 15 nmol / L ), fecal coproporphyrin was 18 nmol / g ( reference : 0 to 45 nmol / g ), and fecal protoporphyrin was 10 nmol / g ( reference : 0–100 nmol / g", "highly increased urine PBG levels, slightly increased plasma porphyrin levels, and normal fecal porphyrin levels", "follow - up brain MRI showed remarkable improvement." ]

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[ "acute pyelonephritis," ]

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[ "a 20 - year - old" ]

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[ "AIP" ]

[ "AIP", "The patient 's abdominal pain resolved in less than 24 h with carbohydrate ( glucose ) loading and highly caloric diet . Therefore , intravenous hemin was not necessary at that time ." ]

[ "short stature for his age ( 131 vs. 154 cm )", "haemoglobin to be 6.7 g / dl." ]

[ "mild hepatomegaly" ]

[ "A 13 - year - old boy born out of a consanguineous marriage presented to the outpatient department with hyperpigmentation and hypertrichosis of lower extremities and trunk for last 4 years. The patient also had hearing loss for more than 5 years which was progressive and was using hearing aid for the same. There was no family history of similar skin changes" ]

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[ "Routine laboratory investigations revealed haemoglobin to be 6.7 g / dl. Liver function tests, thyroid profile, serum cortisol ( 15.25 μg / dL ), and blood sugar were normal. Chest X - ray was normal. Antinuclear antibody was negative. Growth hormone level was reduced to 0.77 ng / ml ( normal range 1–14.4 ng / ml ). Serum Vitamin D3 level ( 51.88 vs. 81–250 nmol / L ) was found to be low. No “ M ” spike was seen in serum protein electrophoresis. Ultrasonography ( USG ) abdomen revealed mild hepatomegaly. USG of scrotum was normal. Contrast enhanced computed tomography head, and orbit revealed bilateral mild axial proptosis. Skin biopsy was taken from the hyperpigmented plaque on the thigh and revealed mild irregular acanthosis, and increased melanin deposition in basal keratinocytes. Significant thickening of collagen bundles in upper and mid - dermis was seen along with perivascular infiltrate of histiocytes. Immunohistochemistry was positive for CD68 and CD45 in dermal perivascular histiocytic infiltrate and for CD34 + in vessel endothelium" ]

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[ "short stature", "Hallux valgus was also present" ]

[ "hearing loss for more than 5 years which was progressive" ]

[ "hyperpigmentation and hypertrichosis of lower extremities and trunk", "well defined, bilaterally symmetrical hyperpigmented, indurated plaques with marked hypertrichosis were present over medial aspect of thighs and legs. Knees and feet were spared. Similar lesions were present over sacral area and lower back bilaterally", "pallor", "Skin biopsy was taken from the hyperpigmented plaque on the thigh and revealed mild irregular acanthosis, and increased melanin deposition in basal keratinocytes. Significant thickening of collagen bundles in upper and mid - dermis was seen along with perivascular infiltrate of histiocytes. Immunohistochemistry was positive for CD68 and CD45 in dermal perivascular histiocytic infiltrate and for CD34 + in vessel endothelium" ]

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[ "13 - year - old" ]

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[ "The final diagnosis of H syndrome was made based on the characteristic clinical and histopathological findings" ]

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[ "His respiratory rate was 50 breaths/ min and was saturating at 99 % in air. His preductal oxygen saturation was 98 % in air and postductal oxygen saturation was 97 % in air" ]

[ "poor feeding", "Examinations of the respiratory system and abdomen were within normal limits" ]

[ "A 10 - day - old male infant presented to the emergency department with a 3 - day history of poor feeding and lethargy. No fever or irritability was noted. He was born at 40 weeks ’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg ( 2nd–9th centile ); length 49.0 cm ( 25th centile ) and head circumference 36.0 cm ( 9th–25th centile ). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of consanguineous parents ( first cousins ) of Bangladeshi descent. He had an older brother who was apparently healthy. There were no chronic diseases that run in the family" ]

[ "poor feeding and lethargy", "No fever or irritability", "crying, alert" ]

[ "His initial blood gas showed the following : pH 7.30 ( 7.35–7.45 ), HCO 3 16.1 mmol / L ( 22–28 mmol / L ), BE −9.0 mmol / L ( −4.0 to +4.0 mmol / L ), Na 112 mmol / L ( 135–145 mmol / L ), K 9.7 mmol / L ( 3.5–5.0 mmol / L ), ionised Ca 1.16 mmol / L ( 1.0–1.3 mmol / L ), glucose 3.9 mmol / L ( 3.0–6.5 mmol / L ) and lactate of 3.3 mmol / L ( < 2 mmol / L )", "An echocardiogram was done, and it was normal", "mutation in CYP21A2 was confirmed by genetic studies" ]

[ "bradycardic", "sunken eyes, normal oral mucosa and a slightly depressed anterior fontanelle", "His preductal oxygen saturation was 98 % in air and postductal oxygen saturation was 97 % in air", "he had a 2/6 systolic murmur best heard in the pulmonary area", "His ECG showed broad complex bradycardia", "repeat ECG showed regular sinus rhythm", "An echocardiogram was done, and it was normal" ]

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[ "hyponatraemia and hyperkalaemia", "genitalia was examined and was noted to have normal male genitalia. The pigmentation of the genitalia was noted to be darker than the infant ’s skin tone" ]

[ "His chest was clear", "Examinations of the respiratory system and abdomen were within normal limits" ]

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[ "He was born at 40 weeks ’ gestation by emergency caesarean section with no complications. He had an Apgar scores of 7, 9 and 9 at 1 min, 5 min and 10 min, respectively. His birth weight was 2.80 kg ( 2nd–9th centile ); length 49.0 cm ( 25th centile ) and head circumference 36.0 cm ( 9th–25th centile ). His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis" ]

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[ "10 - day - old" ]

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[ "A diagnosis of CAH secondary to 21 - hydroxylase deficiency with mutation in CYP21A2 was confirmed by genetic studies ." ]

[ "hydrocortisone intravenously ( 4 mg / kg ) and fludrocortisone acetate ( 50 mcg ) .", ". He was discharged home with oral hydrocortisone ( 2 mg / kg 6 hourly ) , fludrocortisone acetate ( 50 mcg once daily ) and 0.9 % sodium chloride ( 1 mmol / kg twice daily ) ." ]

[ "bilateral thrombosis of the stented SFAs", "acute superficial femoral artery ( SFA ) thrombosis" ]

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[ "Patient 1 ( a woman, 68 years old ) was diagnosed with PXE at 18 years of age. She was referred with a long history of lower limb claudication with an ankle - brachial pressure index ( ABI ) at rest of 0.69 on the right and 0.85 on the left", "Patient 2 ( a woman, 65 years old ) was diagnosed with PXE at 20 years of age. She was referred for severe claudication of the left leg ( < 150 m ) with an ABI of 0.51 and 0.68 on the right.", "Patient 3 was diagnosed with PXE at 8 years of age. At 38 years, the patient underwent her first angioplasty with stenting ( S.M.A.R.T. stent; Cordis, Bridgewater, NJ ) for stenosis of the right SFA", "One year later, a duplex scan disclosed a subtotal stenosis in the right SFA, which was treated by femoral - popliteal saphenous bypass", "angioplasty of the SFA was performed", "again treated by angioplasty", "Patient 4 was diagnosed with PXE at 41 years of age. At 44 years, he complained of severe claudication, and duplex scans showed severe stenosis of both SFAs" ]

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[ "Duplex scan disclosed bilateral calcified short stenosis ( > 70 % ) of the superficial femoral arteries ( SFAs )", "duplex scanning disclosed bilateral thrombosis of the stented SFAs", "Intraoperative angiography demonstrating stenosis of the left superficial femoral artery ( SFA )", "Duplex scans disclosed significant stenosis ( > 70 % ) of the left SFA", "duplex scanning confirmed reocclusion ( ABI, 0.46 ) of the stented SFA", "occlusion of the stented artery was evidenced by duplex scan", "Angiography showing acute superficial femoral artery ( SFA ) thrombosis", "a duplex scan disclosed a subtotal stenosis in the right SFA", "duplex scans revealed restenosis on both sides", "and computed tomography angiography revealed significant restenosis of the left SFA" ]

[ "long history of lower limb claudication with an ankle - brachial pressure index ( ABI ) at rest of 0.69 on the right and 0.85 on the left.", "Duplex scan disclosed bilateral calcified short stenosis ( > 70 % ) of the superficial femoral arteries ( SFAs )", "intermittent claudication recurred", "stenosis of the left superficial femoral artery ( SFA )", "severe claudication of the left leg ( < 150 m ) with an ABI of 0.51 and 0.68 on the right", "Duplex scans disclosed significant stenosis ( > 70 % ) of the left SFA", "A month later, the intermittent claudication recurred, and occlusion of the stented artery was evidenced by duplex scan.", "for stenosis of the right SFA", "duplex scan disclosed a subtotal stenosis in the right SFA", "claudication worsened on the left leg", "in - stent stenosis of the left SFA", "still suffering from claudication", "severe claudication,", "severe stenosis of both SFAs", "maximum walking distance had decreased; duplex scans revealed restenosis on both sides", "Restenosis of the right SFA", "Three years later, his maximum walking distance had declined further ( < 150 m ), and computed tomography angiography revealed significant restenosis of the left SFA" ]

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[ "65 years old" ]

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[ "diagnosed with PXE at 18 years of age .", "diagnosed with PXE at 20 years of age", "was diagnosed with PXE at 8 years of age .", "diagnosed with PXE at 41 years of age ." ]

[ ", 68 years old" ]

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[ "A 32 - year - old, mentally retarded female presented with gait instability and right malar eminence swelling as well as swelling along the posterior aspect of both ankle joints. Patient had undergone surgery for cataracts in both eyes 10 years back." ]

[ "mentally retarded", "gait instability", "ataxia", "hyperintensity of bilateral dentate nuclei, deep cerebellar white matter with hyperintensity of posterior limbs of internal capsules on T2W and FLAIR images with corresponding hypointensity on T1W images. Susceptibility weighted images revealed comma shaped hypointense signal of bilateral dentate nuclei." ]

[ "Lipid profile revealed total cholesterol of 306 mg / dl ( LDL 205 mg / dl, VLDL 46mg / dl, HDL 55 mg / dl ) and triglycerides of 526 mg / dl. Rest of the blood chemistry was normal. Radiograph of ankle joints revealed soft tissue swellings along the posterior aspect of both ankle joints and calcaneal bones. MRI of ankle joints revealed fusiform enlargement of bilateral Achilles tendons with signal intensity similar to muscle with speckled appearance on axial images consistent with tendinous xanthomatosis. MRI brain revealed hyperintensity of bilateral dentate nuclei, deep cerebellar white matter with hyperintensity of posterior limbs of internal capsules on T2W and FLAIR images with corresponding hypointensity on T1W images. Susceptibility weighted images revealed comma shaped hypointense signal of bilateral dentate nuclei. Hyopintense T1W and T2W round lesion was found in subcutaneous tissues of right malar eminence which was subjected to FNAC which revealed a xanthoma. Serum cholestanol levels were raised ( 14 1 micromole / liter )." ]

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[ "fusiform enlargement of bilateral Achilles tendons with signal intensity similar to muscle with speckled appearance on axial images" ]

[ "cataracts in both eyes" ]

[ "right malar eminence swelling as well as swelling along the posterior aspect of both ankle joints", "soft, non - tender swelling along the posterior aspect of both ankle joints, as well as right malar emminence", "tissue swellings along the posterior aspect of both ankle joints and calcaneal bones", "Hyopintense T1W and T2W round lesion was found in subcutaneous tissues of right malar eminence which was subjected to FNAC which revealed a xanthoma" ]

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[ "32 - year - old" ]

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[ "With a combined spectrum of clinical , biochemical and radiological findings , a diagnosis of cerebrotendinous xanthomatosis(CTX ) was made . '" ]

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[ "inflammatory bowel syndrome" ]

[ "A 62 - year - old female patient, a heavy smoker for 40 years and a known case of chronic obstructive pulmonary disease, visited the clinic with a 5 - year history of an asymptomatic eruption on the neck", "no family history of similar skin conditions was recorded, and no history of sun exposure preceded the eruption", "A 68 - year - old female with no significant medical history presented to the clinic with asymptomatic cutaneous lesions for around 16 years", "The patient had no systemic symptoms and was otherwise healthy", "A 61 - year - old female patient presented to the clinic with a 2 - year history of slowly progressive itchy skin lesions after spraying perfumes. Her medical history included diabetes mellitus Type 2, hypertension, asthma, and osteoarthritis", "There was no history of sun exposure or family history of similar cutaneous manifestation", "A 77 - year - old female presented with a 4 - year history of gradual appearance of small skin - colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient 's neck and the upper chest bilaterally. Her medical history included rheumatoid arthritis, psoriasis, inflammatory bowel syndrome, and hypertension", "A 71 - year - old female presented with a 1–2 - year history of asymptomatic skin - colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved. The patient was otherwise healthy, with no other systemic complaints" ]

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[ "Echocardiography was unremarkable", "A skin punch biopsy was performed, and the hematoxylin and eosin ( H and E ) sections revealed a normal - appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered", "H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident" ]

[ "Echocardiography was unremarkable", "hypertension", "hypertension" ]

[ "diabetes mellitus Type 2," ]

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[ "chronic obstructive pulmonary disease", "asthma" ]

[ "osteoarthritis", "rheumatoid arthritis" ]

[ "The ophthalmologic examination was normal", "The eye examination was normal" ]

[ "asymptomatic eruption on the neck.", "numerous soft, oval - to - round, tan papules, measured few millimeters in diameter, with a symmetric distribution around the neck area", "A skin punch biopsy was performed, and the hematoxylin and eosin ( H and E ) sections revealed a normal - appearing epidermis. The dermis was also relatively normal. An elastin stain was performed and revealed the absence of elastic fibers in the papillary dermis. The reticular dermis showed irregular, variably thickened, and distorted elastic fibers. No associated calcification was encountered.", "H and E section and elastin stain revealed increased elastic fibers in the mid and deep dermis, with no calcification being evident", "asymptomatic cutaneous lesions", "numerous tan to yellowish soft papules over the lateral side of the patient 's neck, measuring 2–3 mm", "slowly progressive itchy skin lesions after spraying perfumes.", "multiple symmetrically distributed, skin - colored to yellowish papules, around 2–3 mm, on the lateral and anterior sides of the patient 's neck, upper chest, and the antecubital fossa of both forearms", "gradual appearance of small skin - colored papules, measuring 2–3 mm, with a cobblestone appearance covering the patient 's neck and the upper chest bilaterally.", "psoriasis", "asymptomatic skin - colored to yellow papules coalescing into plaques on both sides of the neck. No other body sites were involved." ]

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[ "62 - year - old", "68 - year - old", "61 - year - old", "77 - year - old", "71 - year - old" ]

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[ "microcytic anemia with hemoglobin levels of 10.1 g / dl, and a platelet count of 5.14 lakhs / cu.mm" ]

[ "hepatomegaly", "hepatomegaly" ]

[ "A 12 - year - old girl, first born of second degree consanguineous marriage presented with a history of hyperpigmentation over the thighs from birth. History of skin thickening over the buttocks, thighs, and legs was present for past 3 months. There was also a history of recurrent fever associated with swelling of legs. History of bilateral hearing loss was present since 5 years of age, and her other developmental milestones were normal. She had attained her menarche at 11 years of age and has had regular menstrual cycles. There was no history of a similar illness in the family" ]

[ "her other developmental milestones were normal", "bilateral sensorineural hearing loss" ]

[ "ESR - 75, CRP - 81, microcytic anemia with hemoglobin levels of 10.1 g / dl, and a platelet count of 5.14 lakhs / cu.mm. Serum protein electrophoresis showed increased gamma fraction of 29.8 suggestive of polyclonal gammopathy. Investigations for the cause of fever revealed no positive findings. Thyroid profile, fasting, and post - prandial blood sugar levels were normal. Anti - nuclear antibodies ’ titer was negative", "Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate", "An ultrasound abdomen revealed hepatomegaly. Chest radiography was normal, and an echocardiography revealed anomalous drainage of left pulmonary vein to innominate vein" ]

[ "swelling of legs" ]

[ "Thyroid profile, fasting, and post - prandial blood sugar levels were normal" ]

[ "menarche at 11 years of age and has had regular menstrual cycles", "normal genitalia" ]

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[ "low height for age", "Skeletal examination was normal" ]

[ "bilateral hearing loss was present since 5 years of age", "proptosis,", "Auditory evaluation revealed bilateral sensorineural hearing loss" ]

[ "hyperpigmentation over the thighs", "skin thickening over the buttocks, thighs, and legs", "proptosis, webbing of neck", "well - defined, bilaterally symmetrical hyperpigmented, indurated plaques with hypertrichosis were present over medial and lateral aspect of thighs and legs sparing knees and feet. Similar lesions were present over the gluteal region bilaterally", "Skin biopsy showed thickened collagen bundles with lymphocytic and histiocytic infiltrates in the dermis extending to the subcutaneous tissue with few areas of fibrosis. Immunohistochemistry studies showed CD68 positivity in dermal perivascular histiocytic infiltrate" ]

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[ "webbing of neck" ]

[ "12 - year - old" ]

[ "birth" ]

[ "we made the diagnosis of H syndrome" ]

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[ "A 52 - year - old Caucasian woman diagnosed with CEP, epilepsy, hypertension, hyperuricemia, and glaucoma on antiglaucoma medication ( Timolol 2 / day ) was referred to our service to assess the performance of a keratoplasty" ]

[ "epilepsy" ]

[ "double homozygous for CEP" ]

[ "hypertension" ]

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[ "glaucoma", "central corneal conjunctivalization of the right eye ( OD ) and the onset of inferior conjunctivalization of the left eye ( OS ). She complained of foreign body sensation, burning, and dryness, accompanied by progressive visual acuity loss in both eyes ( OU", "visual acuity of 0.16 OD and 0.4 OS. Intraocular pressure in OU was 1 6 mm Hg. On slit - lamp examination, the patient presented tear break - up time ( TBUT ) inferior to 1 second, central corneal pannus in OD, and lower epithelial irregularity with less severe conjunctivalization in OS; associated with scales and keratinization of the eyelid margin and complete atrophy of Meibomian glands. Schirmer test value without topical anesthesia was 3 mm in OD and 15 mm in OS. Fluorescein staining was positive with moderate affectation ( grade III ) in the Oxford Squeme", "reported less eye discomfort and bothering with the only remaining signs being conjunctival hyperemia and corneal conjunctivalization. Foreign body sensation and ocular discomfort have decreased and the progress of ocular involvement seems to have slowed down, TBUT persists up to 3 seconds, and fluorescein staining has decreased to minimal ( grade I ) in the Oxford Squeme" ]

[ "intense dermatological lesions on the face and extremities" ]

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[ "52 - year - old" ]

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[ "CEP" ]

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[ "height was 133 centimeters. Her blood pressure was 140/88", "His height was in the fifth centile. His blood pressure was 130/80 mm Hg", "His final height was 139 centimeters" ]

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[ "was referred to our pediatric endocrinology clinic at the age of 16 years when she started to have irregular menstruation.", "Feminizing genitoplasty ( clitoral reccesion ) was performed at the age of 16 years", "Hysterectomy, oophorectomy and a bilateral testicular prosthesis implantation were performed" ]

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[ "normal female karyotype and normal electrolytes. An adrenocorticotropic hormone ( ACTH ) stimulation test showed a baseline cortisol ( F ) level of 28 nmol / L, ACTH of 201 ng / mL ( normal, 0–46 ), 11 - deoxycorticosterone ( 11 - DOC ) of 20 nmol / L ( normal, 0.49–3.3 ), 17 - hydroxyprogesterone ( 17 - OHP ) of 17 nmol / L and testosterone ( T ) of 7 nmol / L. Sixty minutes after the ACTH stimulation test, the F level was 30 nmol / L, the 11 - DOC level was 141 nmol / L ( normal, 2.2–6.8 ) and the 17 - OHP level was 22 nmol / L.", "Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound and a closed epiphyses on a bone age X - ray", "normal female karyotype and normal electrolytes. An ACTH stimulation test showed a baseline F level of 42 nmol / L, an ACTH of 231 ng / mL, 11 - DOC of 40 nmol / L, 17 - OHP of 18 nmol / L and a T level of 7 nmol / L. Sixty minutes after ACTH stimulation, the F level was 45 nmol / L, 11 - DOC was 114 nmol / L and 17 - OHP was 20 nmol / L.", "Radiological evaluation showed a normal uterus and fallopian tubes on ultrasound, normal male urethra on the genitogram and a bone age of 16 years" ]

[ "Her blood pressure was 140/88.", "His blood pressure was 130/80 mm Hg." ]

[ "severe virilized external genitalia : a phallic - like structure with hypospadias and incompletely fused labioscrotal folds", "started to have irregular menstruation", "short male - looking", "Tanner stage IV breast development", "An adrenocorticotropic hormone ( ACTH ) stimulation test showed a baseline cortisol ( F ) level of 28 nmol / L, ACTH of 201 ng / mL ( normal, 0–46 ), 11 - deoxycorticosterone ( 11 - DOC ) of 20 nmol / L ( normal, 0.49–3.3 ), 17 - hydroxyprogesterone ( 17 - OHP ) of 17 nmol / L and testosterone ( T ) of 7 nmol / L. Sixty minutes after the ACTH stimulation test, the F level was 30 nmol / L, the 11 - DOC level was 141 nmol / L ( normal, 2.2–6.8 ) and the 17 - OHP level was 22 nmol / L.", "closed epiphyses on a bone age X - ray.", "short stature, a masculine appearance", "Tanner stage IV pubic hair and stage II breast development", "An ACTH stimulation test showed a baseline F level of 42 nmol / L, an ACTH of 231 ng / mL, 11 - DOC of 40 nmol / L, 17 - OHP of 18 nmol / L and a T level of 7 nmol / L. Sixty minutes after ACTH stimulation, the F level was 45 nmol / L, 11 - DOC was 114 nmol / L and 17 - OHP was 20 nmol / L.", "bone age of 16 years" ]

[ "severe virilized external genitalia : a phallic - like structure with hypospadias and incompletely fused labioscrotal folds", "Genital examination showed a phallus 7 centimeters in stretched length, a single perineal orifice and incompletely fused labioscrotal folds. No gonads were palpable", "normal uterus and fallopian tubes on ultrasound", "cystoscopy showed that her vaginal communication was just below the bladder neck and high in the urogenital sinus", "named as a boy based on the appearance of the external genitalia", "Genital examination showed a phallus 7 centimeters in stretched length, a normal meatal opening at the tip of the glans penis with no hypospadias, and completely fused labioscrotal folds but the gonads were palpable", "normal uterus and fallopian tubes on ultrasound, normal male urethra on the genitogram" ]

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[ "closed epiphyses on a bone age X - ray", "bone age of 16 years" ]

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[ "acne", "acne" ]

[ "She was a product of a full - term spontaneous vaginal delivery at home", "He was born at home" ]

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[ "20 years old" ]

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[ "she was diagnosed as having 11 - hydroxylase deficiency", "He was diagnosed as having 11 - hydroxylase deficiency" ]

[ "was started on hydrocortisone 10 mg twice a day", "started on hydrocortisone 10 mg twice a day ." ]

[ "Vital signs Pulse rate, 83 beats per minute; blood pressure, 100/70 mmHg; respiratory rate, 13 breaths per minute; and temperature, 37 ° C Anthropometric parameters Weight, 47.1 kg; height, 160 cm; MUAC, 19.3; BMI, 18.4; height / age, -1.7 SD; BMI / age, -0.9 SD" ]

[ "Mild hepatosplenomegaly", "mild hepatosplenomegaly" ]

[ "A 16 - year - old Iraqi boy, born of first - cousin parents, presented to our outpatient clinic at Al - Sadr Teaching Hospital with hyperpigmented patches symmetrically overlying with hypertrichosis involving the inner aspects of his thighs. These lesions progressed slowly over 6 years, starting first as hypertrichosis and then with indurated hyperpigmented patches gradually developing. He also had hearing loss, speaking difficulties, premature graying of the hair, gynecomastia, corneal arcus, hypospadias, and finger and toe deformities ( hallux valgus ). These features started at age 10, except for the hypospadias, which was present since birth, and the hearing loss and speaking difficulties, which were diagnosed in early childhood. The mother stated that the child delayed walking until the age of 2 years, and she reported that he had a severe ear infection by the age of 6. The patient has 3 brothers and 2 sisters; his older brother has bilateral swelling of the feet and deformities of the toes, but the patient 's other siblings are all healthy" ]

[ "speaking difficulties", "speaking difficulties", "delayed walking until the age of 2 years", "brain magnetic resonance imaging was normal" ]

[ "elevated erythrocyte sedimentation rate of 93 ( normal range, 0–15 mm / h ), elevated serum cortisol of 1030 nmol / L ( normal range at morning, 171 - 536 nmol / L ), and decreased serum testosterone level of 2.63 ng / mL ( normal range, 2.8 - 8 ng / mL ). Complete blood count showed mild microcytic anemia. Thyroid function tests, liver function tests, renal function tests, serum electrolytes, vitamin B12, serum ferritin, serum iron, antinuclear antibodies, anti – double - stranded DNA, anti - cyclic citrullinated peptide, and lipid profile all were normal", "Echocardiography and electrocardiogram were normal, abdominal ultrasound scan found mild hepatosplenomegaly, brain magnetic resonance imaging was normal", "Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes", "Immunohistochemistry stain shows diffuse infiltration of histiocytes" ]

[ "nonpitting edema of the ankles" ]

[ "gynecomastia", "pubic hair presents in normal distribution", "elevated serum cortisol of 1030 nmol / L ( normal range at morning, 171 - 536 nmol / L ), and decreased serum testosterone level of 2.63 ng / mL ( normal range, 2.8 - 8 ng / mL )" ]

[ "hypospadias", "hypospadias", "Hypospadias; pubic hair presents in normal distribution; scrotal examination is normal" ]

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[ "finger and toe deformities ( hallux valgus )", "Bilateral hallux valgus deformity, with fixed flexion contractures, in the interphalangeal joints of the toes and the little fingers", "Hallux valgus deformity, with flexion contractures of the toes and little fingers" ]

[ "hearing loss, speaking difficulties", "corneal arcus", "hearing loss and speaking difficulties", "ears are of abnormal shape and size. Eyes Bilateral corneal arcus; moderate exophthalmos; asymmetrical corneal light reflex. Ophthalmoscopic examination showed bilateral swelling of the optic disc. Visual acuity is normal. Hearing assessment Severe hearing loss", "pure tone audiometry found bilateral profound mixed hearing loss" ]

[ "hyperpigmented patches symmetrically overlying with hypertrichosis involving the inner aspects of his thighs. These lesions progressed slowly over 6 years, starting first as hypertrichosis and then with indurated hyperpigmented patches gradually developing", "premature graying of the hair", "Large hyperpigmented indurated patches overlying with hypertrichosis, symmetrically involving the medial aspects of the thighs and extending to the posterior aspects of the legs. The dorsa of the feet are also involved with well - demarcated, large, hyperpigmented patches. However, the pigmented patches spare the buttocks and knees ( see Fig 1 ). There are both hypo- and hyperpigmented lesions on the face, neck, and upper chest. Hair Shows salt - and - pepper gray hair", "face looks flat; ears are of abnormal shape and size", "Bilateral gynecomastia", "Large, hyperpigmented patches overlying symmetrically with hypertrichosis involving the inner aspect of the thighs, both calves, and the dorsa of the feet, while sparing the knees", "salt - and - pepper gray hair", "Histopathology findings showed widespread fibrosis and thickened collagen bundles in the papillary and mid dermis and striking infiltrates of CD68 + histiocytes", "Immunohistochemistry stain shows diffuse infiltration of histiocytes" ]

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[ "Lymph nodes Severely enlarged inguinal lymph nodes, with tenderness on palpation" ]

[ "16 - year - old" ]

[ "These features started at age 10 , except for the hypospadias , which was present since birth , and the hearing loss and speaking difficulties , which were diagnosed in early childhood" ]

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[ "her blood pressure was 136/101 mm Hg, and her heart rate was 109 / min", "moderately increased blood pressure ( 159/101 mm Hg ) and tachycardia ( 112 / min )" ]

[ "ileus", "abdominal pain as well as constipation", "recurrent abdominal pain", "her abdominal pain regressed", "Unexplained abdominal pain", "abdominal and lumbar pain lasting for 12 days after heavy food and alcohol intake before 1 week", "acute pancreatitis", "paroxysmal pain was not relieved", "recurrent severe paroxysmal abdominal and lumbar pain", "severe recurrent abdominal pain" ]

[ "An 18 - year - old girl was admitted to our hospital following development of generalized tonic - clonic seizure in November 2016.", "In December 2014, a 27 - year - old man was admitted to our hospital for abdominal and lumbar pain lasting for 12 days after heavy food and alcohol intake before 1 week." ]

[ "generalized tonic - clonic seizure", "brain MRI was performed in her local hospital indicating PRES", "seizures", "seizures", "no focal neurological deficit", "hallucination", "The cerebral spinal fluid ( CSF ) analysis was normal", "Brain MRI performed in our hospital 6 days later revealed partial resolution", "No seizures occurred", "repeat brain MRI performed in her local hospital confirmed the total disappearance of the lesions", "seizures and PRES on brain magnetic resonance imaging ( MRI", "seizures", "generalized tonic - clonic seizure occurred. Then, partial seizures in the left limb continued", "decreased tendon reflex in the 4 limbs", "Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1 - weighted images and were hyperintense on T2 - weighted and fluid - attenuated inversion recovery images. Diffusion - weighted images ( DWI ) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient ( ADC ) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES ( Fig. 1 ). There was mild contrast enhancement", "Electroencephalography showed diffuse slow waves without epileptiform discharges", "The results of the cerebrospinal fluid analysis were normal" ]

[ "and a series of tests including abdominal X - ray, CT scan, and ultrasound were normal", "Except for remarkable hyponatremia of 104 mmol / L, her serum potassium was 3.0 mmol / L, aspartate transaminase 243 U / L, alanine transaminase 142 U / L, and total bilirubin 37 μmol / L. Tests for antinuclear and anticardiolipin antibodies were normal. The patient was sero - negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The cerebral spinal fluid ( CSF ) analysis was normal. Tests for heavy metal toxins including lead, mercury, and arsenic were also negative. Brain MRI performed in our hospital 6 days later revealed partial resolution", "3 repeated urine Watson – Schwartz tests", "PRES on brain magnetic resonance imaging ( MRI ).", "diagnosis was made after repeated Watson – Schwartz tests.", "No abnormalities were found in his abdominal computed tomography ( CT ) and X - ray.", "His creatine kinase was 246 U / L ( normal, 0–170 U / L ), aspartate transaminase was 42 U / L ( 15–40 U / L ) and serum sodium was 130 mmol / L ( normal, 137–147 mmol / L ). Other biochemistry tests were not suggestive. Tests for connective tissue disorders, viral infection, heavy metal poisoning, thyroid function, and antithyroid antibodies were all negative. Brain MRI demonstrated multifocal lesions in the bilateral occipitoparietal and frontal lobes. The lesions were hypointense on T1 - weighted images and were hyperintense on T2 - weighted and fluid - attenuated inversion recovery images. Diffusion - weighted images ( DWI ) were hypointense, and some were patchy hyperintense, while apparent diffusion coefficient ( ADC ) maps were hyperintense, which was suggestive of vasogenic edema instead of cytotoxic edema in PRES ( Fig. 1 ). There was mild contrast enhancement", "The results of the cerebrospinal fluid analysis were normal.", "3 repeated positive urine Watson – Schwartz tests for porphobilinogen ( PBG ). His urine turned dark and red upon exposure to light" ]

[ "blood pressure increased", "moderately increased blood pressure ( 159/101 mm Hg ) and tachycardia ( 112 / min )" ]

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[ "lumbar pain", "lumbar pain" ]

[ "no complaint of visual disturbance" ]

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[ "18 - year - old", "27 - year - old" ]

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[ "AIP was confirmed", "AIP", "The diagnosis of AIP" ]

[ "The patient was given a high carbohydrate diet and intravenous dextrose . No hematin was available for her", "Hematin", "Glucose infusion and a high carbohydrate diet were given to the patient , as hematin was not available" ]

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[ "A 20 - year - old male presented with a gradually increasing swelling of the left testis for 1 year duration" ]

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[ "Ultrasonography showed bilateral enlargement of the testes and epididymes ( right testis measuring 41 ml in volume ( 6.6 cm × 3.7 cm × 2.3 cm ), left testis measuring 52.1 ml in volume ( 6.2 cm × 4.5 cm × 3.6 cm ) ). In addition, there were bilateral grade - II varicocele. Seminal fluid analysis showed azoospermia", "A biopsy of the right epididymis was performed. The sections revealed nodules of cells with intervening dense fibrous septae. The nodules comprised nests and cords of polygonal Leydig cells with abundant eosinophilic cytoplasm, uniform round nuclei and small nucleoli. Cell borders were distinct and a lymphoid infiltrate was present in the stroma ( Fig. 1 ). Testicular tissue comprised of seminiferous tubules with thickened basement membranes. Residual testicular tissue showed predominantly germ cell aplasia with occasional tubules containing spermatogonia. Most seminiferous tubules contained only Sertoli cells. Spermatocytes, spermatids and spermatozoa were absent. Collections of Leydig cells were noted between the seminiferous tubules. Intratubular germ cell neoplasia or malignancy was absent ( Fig. 2 ). Special stains with Mason trichrome did not show Reinke crystals. The cells displayed diffuse cytoplasmic positivity for synaptophysin" ]

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[ "gradually increasing swelling of the left testis", "large hard indurated swelling of both epididymes more prominent on the left side. Left testis was ill - defined with an approximate diameter of 3.5 cm", "Ultrasonography showed bilateral enlargement of the testes and epididymes ( right testis measuring 41 ml in volume ( 6.6 cm × 3.7 cm × 2.3 cm ), left testis measuring 52.1 ml in volume ( 6.2 cm × 4.5 cm × 3.6 cm ) ). In addition, there were bilateral grade - II varicocele. Seminal fluid analysis showed azoospermia", "A biopsy of the right epididymis was performed. The sections revealed nodules of cells with intervening dense fibrous septae. The nodules comprised nests and cords of polygonal Leydig cells with abundant eosinophilic cytoplasm, uniform round nuclei and small nucleoli. Cell borders were distinct and a lymphoid infiltrate was present in the stroma ( Fig. 1 ). Testicular tissue comprised of seminiferous tubules with thickened basement membranes. Residual testicular tissue showed predominantly germ cell aplasia with occasional tubules containing spermatogonia. Most seminiferous tubules contained only Sertoli cells. Spermatocytes, spermatids and spermatozoa were absent. Collections of Leydig cells were noted between the seminiferous tubules. Intratubular germ cell neoplasia or malignancy was absent ( Fig. 2 ). Special stains with Mason trichrome did not show Reinke crystals. The cells displayed diffuse cytoplasmic positivity for synaptophysin", "marked reduction in the sizes of testes with minimal induration" ]

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[ "20 - year - old" ]

[ "age of 1 year" ]

[ "He was diagnosed to have CAH at the age of 1 year" ]

[ "A course of prednisolone was started and there was good response ." ]