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cxyzhang

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caseReportBench_ClinicalDenseExtraction_Benchmark

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[ "standing height of 153.4 cm ( z score : −3.1 )" ]

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[ "A 28 - year - old man with classic salt - wasting CAH due to 21 - hydroxylase deficiency presented with subfertility. He had known bilateral TARTs" ]

[ "insomnia" ]

[ "A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ), and semen analysis showed azoospermia.", "Biochemical evaluation at 0800 before medication showed 17 - hydroxyprogesterone 13,060 ng / dL ( reference : 13 to 120 ng / dL ), androstenedione ( A4 ) 1025 ng / dL ( reference : 26 to 125 ng / dL ), ACTH 866 pg / mL ( reference : 5 to 46 pg / mL ), plasma renin activity ( PRA ) 7.1 ng / mL / h ( reference : 0.6 to 4.3 ng / mL / h ), FSH 1.7 U / L ( reference : 1 to 11 U / L ), LH 1.3 U / L ( reference : 1 to 8 U / L ), and total testosterone ( T ) 473 ng/ dL ( reference : 240 to 950 ng / dL ). His A4 / T ratio of 2.2 ( > 0.5 ) with low LH and FSH was suggestive of a mostly adrenal origin of his T.", "Repeat ultrasound showed 91 % decrease in total TART volume ( 0.47 mL ) ( Fig. 1 ). Follow - up semen analysis showed a sperm count of 132 × 10 6 /mL ( reference range : > 14 × 10 6 /mL ), with 7 × 10 6 /mL being morphologically normal ( reference range : > 3 × 10 6 /mL ) and 35 % motile ( normal > 39 % ). Biochemical evaluation showed significant improvement in CAH control, with 0800 evaluation before medication revealing 17 - hydroxyprogesterone 66 ng / dL, A4 16 ng / dL, ACTH 13.5 pg / mL, PRA 11 ng / mL / h, FSH 5.4 U / L, LH 1 U / L, and T 287 ng / dL", "CYP21A2 genotyping was performed. Our patient had a 30 - kb deletion ( CH-1 chimera subtype ) in one allele and IVS2 - 13A / C > G ( In2 G ) mutation in the second allele" ]

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[ "subfertility", "bilateral TARTs, first noted at age 18 and occupying 1.2 % of his total testicular volume ( 0.38 mL of 30.68 mL )", "A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ),", "short - statured", "17 - hydroxyprogesterone 13,060 ng / dL ( reference : 13 to 120 ng / dL ), androstenedione ( A4 ) 1025 ng / dL ( reference : 26 to 125 ng / dL ), ACTH 866 pg / mL ( reference : 5 to 46 pg / mL ), plasma renin activity ( PRA ) 7.1 ng / mL / h ( reference : 0.6 to 4.3 ng / mL / h ), FSH 1.7 U / L ( reference : 1 to 11 U / L ), LH 1.3 U / L ( reference : 1 to 8 U / L ), and total testosterone ( T ) 473 ng/ dL ( reference : 240 to 950 ng / dL ). His A4 / T ratio of 2.2 ( > 0.5 ) with low LH and FSH", "weight gain of 5 kg", "91 % decrease in total TART volume ( 0.47 mL )", "17 - hydroxyprogesterone 66 ng / dL, A4 16 ng / dL, ACTH 13.5 pg / mL, PRA 11 ng / mL / h, FSH 5.4 U / L, LH 1 U / L, and T 287 ng / dL", "weight gain", "lost 3 kg" ]

[ "subfertility", "bilateral TARTs, first noted at age 18 and occupying 1.2 % of his total testicular volume ( 0.38 mL of 30.68 mL )", "A recent testicular ultrasound showed increased TART volume, now occupying 16 % of his total testicular volume ( 5.01 mL of 32.30 mL testicular volume ), and semen analysis showed azoospermia.", "Testicular volume was 25 mL bilaterally", "Testicular volume was stable at 25 mL.", "91 % decrease in total TART volume ( 0.47 mL ) ( Fig. 1 ). Follow - up semen analysis showed a sperm count of 132 × 10 6 /mL ( reference range : > 14 × 10 6 /mL ), with 7 × 10 6 /mL being morphologically normal ( reference range : > 3 × 10 6 /mL ) and 35 % motile ( normal > 39 % )." ]

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[ "On examination, the patient was short - statured, with a standing height of 153.4 cm ( z score : −3.1 ); midparental height was 174.1 cm ( z score : −0.4 )." ]

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[ "supraclavicular fullness with predominantly central weight gain and the presence of abdominal striae" ]

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[ "28 - year - old" ]

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[ "with classic salt - wasting CAH due to 21 - hydroxylase deficiency" ]

[ "He had been receiving prednisone 5 mg each morning and fludrocortisone 50 μg twice daily over the last decade", "His glucocorticoid therapy was switched from prednisone 5 mg daily to dexamethasone 250 μg at bedtime to suppress the nocturnal ACTH surge ." ]

[ "143 cm/49 kg, body surface area 1.37 m 2", "her initial systolic blood pressure and heart rate were 131 mmHg and 68 beats per minute, respectively. Her blood pressures were almost equal in the upper and lower extremities", "Her initial hemoglobin level was 11.8 g / dL" ]

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[ "A 32 - year - old woman with Turner syndrome ( 143 cm/49 kg, body surface area 1.37 m 2 ) was admitted to Kyungpook National University Hospital center with complaint of sudden - onset back pain" ]

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[ "Her initial hemoglobin level was 11.8 g / dL", "An initial computed tomography ( CT ) scan revealed intimal dissection on aortic isthmus level and a dissected flap extending from the left subclavian artery to the descending aorta. An elongated transverse aortic arch ( ETA ) and an aberrant right subclavian artery ( ARSA ) branching into the aortic isthmus as unusual anatomic location were seen. Periaortic hematoma formation was suspected of possible extravasation. In addition, a partial anomalous pulmonary venous connection ( PAPVC ) showed that the vertical vein connected to the left upper lobe drained into the left bra - chiocephalic vein", "Subsequent CT scan revealed active aggravation of ruptured aortic dissection and aneurysmal dilatation on dissected aorta. The false lumen had increased in size to 10 % of the aortic maximum diameter, measuring 3.9 cm, and left pleural fluid collection suspicious to hemothorax and periaortic hematoma had increased", "CT scan revealed a well - functioning aortic isthmus stent graft without endoleaks, and complete occlusion of both subclavian artery orifices with distal run - off reserved from collateral flow" ]

[ "sudden - onset back pain", "electrocardiography revealed a normal sinus rhythm" ]

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[ "short stature" ]

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[ "32 - year - old" ]

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[ "Turner syndrome" ]

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[ "vomiting" ]

[ "This child presented with encephalopathy, fatigue, muscle weakness, ketonuria, and lipid storage in muscles", "Our patient is a 13 - year - old boy who was the second child born to non - consanguineous parents. He noticed tiredness and pain in muscles on walking. Patient had about 6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking. He also had vomiting and brown colored urine after exertion" ]

[ "encephalopathy, fatigue, muscle weakness", "All reflexes were preserved and sensations were normal" ]

[ "ketonuria", "His tandem mass spectroscopy showed elevated medium - chain acylcarnitine and long - chain acylcarnitine suggestive of MADD. His urine showed elevated excretion of 2HG, adipate, and arabitol", "Investigations showed severe ketonuria ( creatine kinase, 1271 IU / L, lactate dehydrogenase, 2622 IU / L ). Liver and renal function tests were normal ( aspartate transaminase, 1214 IU / L; alalnine transaminase, 307 IU / L; potential of Hydrogen, 7.4; partial pressure of Carbon Dioxide, 39.9; partial pressure of Oxygen, 77.4; lactate, 2.8 µmol / L ). Ultrasonography of abdomen was normal. Estimation of blood levels of free acylcarnitines by tandem mass spectrometry showed significant elevation of short, medium and long - chain acylcarnitines suggestive of multiple acyl - CoA dehydrogenase deficiency. The following levels were obtained from the estimation : hexanoylcarnitine ( C6)- 0.67 μmol / L ( normal range 0–0.23 μmol / L ); adipylcarnitine ( C6DC)- 0.52 μmol / L ( normal range 0.01–0.33 μmol / L ); octanylcarnitine ( C8 ) I-1.2 μmol / L ( normal range 0.01–0.39 μmol / L ); decanoylcarnitine ( C10)-1.71 μmol / L ( normal range 0–0.5 μmol / L ); dodecanoylcarnitine ( C12)-0.63 μmol / L ( normal range 0.02–0.42 μmol / L ); tetradecanoylcarnitine ( C14)- 0.56 μmol / L ( normal range 0.03–0.41 μmol / L ) and tetradecanoylcarnitine ( C14)- 0.59 μmol / L ( normal range 0.01–0.28 μmol / L ). Profiling of urine organic acids showed increased excretion of 2 - hydroxyglutarate ( 2HG ), adipate, arabitol, and 3 - hydroxy butyrate. Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin – stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O – positive material suggesting lipid storage." ]

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[ "thin built child with a small goiter" ]

[ "brown colored urine after exertion" ]

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[ "muscle weakness", "lipid storage in muscles", "tiredness and pain in muscles on walking", "6 episodes of weakness of all four limbs presenting as difficulty in getting up from sitting posture and falls while walking", "brown colored urine after exertion", "Wasting of supraspinatus, infraspinatus, deltoid, and pectoralis muscles was reported with winging of scapula. Power was 4/5 in proximal muscles of upper limbs and 2 to 3/5 in lower limbs", "creatine kinase, 1271 IU / L", "Muscle biopsy was carried out and histopathological analysis of transversely cut skeletal muscle tissue showed mild variation in fiber diameter and multiple fine vacuoles in hematoxylin and eosin – stained material. Modified Gomori trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stain showed vacuolated fibers with Oil Red O – positive material suggesting lipid storage" ]

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[ "13 - year - old" ]

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[ ". The patient was started on high carbohydrate diet with restriction on protein , fat and started on riboflavin ( 200 mg ) and carnitine ( 1.5 g ) per day ." ]

[ "HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats / min", "HR increased by 45 to 120 beats / min", "twin 2 exhibited a diastolic blood pressure ( DBP ) that exceeded the threshold for sex and height and had DBP readings 20 % higher than those of twin 1", "Wt. ( kg ) 43.6 46.0 Ht. ( cm ) 152.3 154.8 BMI percentile ( for age and sex ) ( kg / m 2 ) 25th 40th Resting BP ( mm Hg ) 118/70 123/84" ]

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[ "Monozygotic female adolescent twins, aged 16 years old, were originally diagnosed in infancy with NC and found to have a 57 - kb deletion of the CTNS gene, the most frequent cause of NC in Western populations.", "Both twins were transplanted 6 years previously with kidneys from a single deceased donor source. Since that time, both twins experienced several episodes of transplant rejection, whereas twin 1 also developed Epstein - Barr virus positive posttransplant proliferative disorder" ]

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[ "Measured GFR ( ml / min per 1.73 m 2 ) 59.3 70.0", "Tacrolimus level ( ng / ml ) 5.5 4.5", "Creatinine, blood urea nitrogen, and cystatin C levels were consistent with the CKD stage of each twin. Both patients also had blood drawn for measurement of their leukocyte cystine levels, which were obtained at the time of their regular laboratory tests. Those results were 1.65 and 1.90 nmol 1/2 cystine per milligram per protein for twins 1 and 2, respectively", "Cr BUN Cystatin C Alb Phos Na K Glucose 1 1.08 ( 95.47 ) 15 ( 5.35 ) ( 1.25 ) 4.5 ( 45 ) 3.7 ( 1.20 ) 136 ( 136 ) 4.0 ( 4.0 ) 98 ( 5.44 ) 2 0.81 ( 71.60 ) 13 ( 4.64 ) ( 1.09 ) 4.9 ( 49 ) 3.8 ( 1.23 ) 137 ( 137 ) 4.2 ( 4.2 ) 94 ( 5.22 ) Normal reference range 0.25−1.14 mg / dl 5.0−18.0 mg / dl 0.5−1.3 mg / l ( 1−17 yr ) 3.6−4.7 g / dl 3.0−4.8 mg / dl 134−146 mEq / l 3.7−5.7 mEq / l 60−110 mg / dl SI units normal Reference Range 22.1−100.78 mmol / l 1.78−6.43 mmol / l 0.50−1.30 mg / l 36.0−47.0 g / l 0.97−1.55 mmol / l 134−146 mmol / l 3.7−5.7 mmol / l 3.33−6.11 mmol / l" ]

[ "HR of twin 1 exhibited a compensatory increase to a maximum of 110 beats / min at 6.9 minutes into the HUT and remained at this level until she was returned to a horizontal and/or supine position. This was a change of 52 beats / min. In Figure 1 b, a systolic BP ( SBP ) decline of 29.8 mm Hg can be seen at 0.3 minutes into the HUT. The BP of twin 1 recovered quickly to pre - HUT levels and remained stable thereafter throughout the 10 - minute HUT. Conversely, for twin 2, HR increased by 45 to 120 beats / min and a 30 - mm Hg SBP drop occurred when transitioned from a supine position to a 70 ° HUT ( Figure 1 c and d ). In addition, the HR and SBP remained at these levels throughout the HUT until the twin returned to the supine position. Thus, both twins exhibited orthostatic tachycardia during HUT that was maintained until returning to the supine horizontal body position, which indicated a greater than average response compared with normative data", "cold hands and feet before warming", "symmetric warming of their hands but their feet remained slightly cooler", "twin 2 exhibited a diastolic blood pressure ( DBP ) that exceeded the threshold for sex and height and had DBP readings 20 % higher than those of twin 1.", "heat intolerance" ]

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[ "cystine crystal accumulation in the lens and cornea", "photophobia secondary to corneal cystine crystal deposition" ]

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[ "16 years old" ]

[ "infancy" ]

[ "diagnosed in infancy with NC and found to have a 57 - kb deletion of the CTNS gene , the most frequent cause of NC in Western populations ." ]

[ "They were on cysteamine bitartrate ( cystagon - immediate release ) since diagnosis . Each was currently prescribed Procysbi ( cysteamine - delayed release ) 675 mg every 12 hours . In addition , each twin was prescribed cysteamine hydrochloride ( 0.44 % ) eye drops due to cystine crystal accumulation in the lens and cornea . Both twins were transplanted 6 years previously with kidneys from a single deceased donor source ." ]

[ "coagulopathy", "Ferritin level was elevated at 8,397 umol / L.", "normal ammonia level and clotting profile all along", "Ferritin level was high at 9,801 umol / L." ]

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[ "The baby presented with recurrent hypoglycemia shortly after birth" ]

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[ "Blood tests on the second day of life showed cholestasis ( up to 145 umol / L ), hypoalbuminemia, hyperammonemia ( up to 453 umol / L ), and coagulopathy, which progressively worsened throughout the first week of life. Work - up for neonatal liver failure was negative for metabolic disease, and surgical and infective causes. Ferritin level was elevated at 8,397 umol / L.", "Biopsy of the liver and buccal mucosa was performed. This demonstrated hepatic and extrahepatic iron deposition", "Her liver function test showed mildly elevated liver enzymes ( peak aspartate aminotransferase of 371 U / L and alanine aminotransferase of 162 U / L at around 3 weeks of life ) and conjugated bilirubin ( 11 umol / L ), with normal ammonia level and clotting profile all along. Metabolic, surgical, and infective work - ups were negative. Ferritin level was high at 9,801 umol / L. Liver function test subsequently normalized spontaneously upon follow - up." ]

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[ "recurrent hypoglycemia" ]

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[ "A dichorionic diamniotic male twin was born at 35 weeks of gestation with a birth weight of 1.6 kg ( small for gestational age ).", "the other twin girl was born with a birth weight of 2.4 kg" ]

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[ "shortly after birth" ]

[ "shortly after birth" ]

[ "confirmed the diagnosis of neonatal hemochromatosis ( NH ; likely due to gestational alloimmune liver disease , GALD ) ." ]

[ "Medical treatment was given with exchange transfusion and intravenous immunoglobulin ( IVIg )" ]

[ "Her height was 154 cm, weight 48 kg" ]

[ "hepatomegaly", "marked hepatomegaly", "hepatic dysfunction", "abdominal pains" ]

[ "apparent reduction of the subcutaneous adipose tissue at 1 mo of age", "Poor weight gain was seen during a health checkup at 3 mo of age" ]

[ "An intelligence test ( WISC - IV ) at 12 yr of age demonstrated that his full - scale intelligence quotient was 58, indicating slightly retarded mental development with mild intellectual disability", "insomnia, headaches", "her psychological state that is in line with her school year", "headaches and insomnia gradually decreased" ]

[ "Laboratory examination demonstrated extremely high triglyceride level and low leptin level ( Table 1 ). Compound heterozygous variants of BSCL2 gene were identified; these were identical to the gene variants found in his sister", "Serum triglyceride and insulin levels increased to more than 2000 mg / dL and 700 μU / mL, respectively, at 2 mo of age", "notable hyperinsulinemia and hypertriglyceridemia", "Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy. The serum leptin concentration was markedly low ( 0.9 ng / mL ) ( 13 ). Genetic testing revealed compound heterozygous pathogenic variants of BSCL2 gene; the already reported variant ( c.823C > T ) and the unreported variant ( c.576C > A )", "oral glucose tolerance test ( OGTT ) showed diabetic glucose response (", "aggravation of her HbA1c and triglyceride levels", "HbA1c level was 6.0 % in a stable state" ]

[ "Cardiac ultrasonography demonstrated hypertrophic cardiomyopathy" ]

[ "extremely high triglyceride level and low leptin level", "Serum triglyceride and insulin levels increased to more than 2000 mg / dL and 700 μU / mL, respectively, at 2 mo of age", "hyperlipidemia and hyperinsulinemia resolved", "His insulin resistance worsened and his triglyceride level increased during puberty", "hyperinsulinemia and hyperlipidemia", "hyperinsulinemia", "Poor weight gain", "notable hyperinsulinemia and hypertriglyceridemia", "The serum leptin concentration was markedly low ( 0.9 ng / mL ) ( 13 ).", "marked insulin resistance", "insulin resistance and lipid metabolism also worsened", "hyperglycemia with hyperinsulinemia gradually deteriorated", "diabetic glucose response", "aggravation of her HbA1c and triglyceride levels", "irregular menstruation" ]

[ "irregular menstruation" ]

[ "obstructive sleep apnea" ]

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[ "apparent reduction of the subcutaneous adipose tissue", "inverted triangular face, sparse subcutaneous tissue", "generalized reduction in the subcutaneous adipose tissue" ]

[ "born at 36 wk of gestational age", "born to non - consanguineous Japanese parents at 38 wk of gestational age" ]

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[ "16 yr and 4 mo of age" ]

[ "1 mo of age .", "3 mo of age" ]

[ "CGL", "She was therefore diagnosed with CGL ( Berardinelli - Seip syndrome ) ." ]

[ "At 11 yr and 6 mo of age , metreleptin was introduced at a dose of 0.04 mg / kg / d , and there was an immediate improvement of hyperinsulinemia and hyperlipidemia", "At 11 yr and 5 mo of age , she was enrolled in a clinical trial of metreleptin . Metreleptin treatment was initiated at a dose of 0.06 mg / kg / d. Marked effectiveness of metreleptin appeared as early as 1 mo after the initiation" ]

[ "( height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg / m 2 )", "height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg / m 2", "height=94 cm, z -score=-0.05, 48th percentile; weight=14 kg, z -score=0.03, 51st percentile; BMI=15.8 kg / m 2", "height=158 m, z -score=-0.7, 23rd percentile; weight=73.6 kg, z -score=1.4, 92nd percentile; BMI=29.5 kg / m 2" ]

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[ "The proband was a male born to consanguineous parents ( Fig. 1 ). He had an acute viral fever at 4 years of age, and was found to have mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively )", "no history of prostration with illness, and normally - timed pubertal changes", "the 3 - year - old sister was screened for increased 17 - OHP and ACTH levels, which were found to be mildly elevated", "no history of virilization, precocious puberty or prostration with illness", "family studies indicated that the father had the same genotype as the 2 children, with one copy deleted and the other harboring the p. R124C mutation. The mother was heterozygous for the large deletion." ]

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[ "mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively ). Further investigation revealed increased 17 - hydroxyprogesterone ( 17 - OHP ) and adrenocorticotropic hormone ( ACTH ) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1 - 24 stimulation ( 13.4 μg / dL after 60 minutes )", "screened for increased 17 - OHP and ACTH levels, which were found to be mildly elevated", "ACTH1 - 24 -stimulation showed suboptimal rise in cortisol levels ( 13.12 μg / dL after 60 minutes )", "normal serum electrolytes, mildly increased ACTH and stimulated 17 - OHP levels", "Molecular testing revealed that the proband had one deleted copy of CYP21A2, whereas the other copy harbored a likely pathogenic sequence variant ( c.748C > T, p. R124C )", "with mild, expected laboratory derangements, proband ’s sister had a 17 - OHP levels ( 9,072 ng / dL )" ]

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[ "mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively ). Further investigation revealed increased 17 - hydroxyprogesterone ( 17 - OHP ) and adrenocorticotropic hormone ( ACTH ) levels ( Table 1 ), and a suboptimal rise in cortisol levels following ACTH1 - 24 stimulation ( 13.4 μg / dL after 60 minutes ).", "normal growth and stature", "no evidence of precocious adrenarche or puberty", "no history of prostration with illness, and normally - timed pubertal changes", "obese with normal stature", "normal testes with Tanner stage V pubic hair", "screened for increased 17 - OHP and ACTH levels, which were found to be mildly elevated", "normal growth and stature", "ACTH1 - 24 -stimulation showed suboptimal rise in cortisol levels ( 13.12 μg / dL after 60 minutes ).", "no history of virilization, precocious puberty or prostration with illness", "obese", "with no hirsutism and normal female genitalia ( Tanner V breasts and pubic hair", "normal serum electrolytes, mildly increased ACTH and stimulated 17 - OHP levels", "had a 17 - OHP levels ( 9,072 ng / dL )" ]

[ "mild hyponatremia and hyperkalemia ( sodium 131 mEq / L and potassium 6.1 mEq / L, respectively )", "normal male genitalia, descended testes, and no evidence of precocious adrenarche or puberty", "normal testes with Tanner stage V pubic hair", "normal serum electrolytes" ]

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[ ". At the time of diagnosis proband was of normal growth and stature ( height=107 cm, z -score=-0.4, 32nd percentile; weight=20.8 kg, z -score=+0.8, 80th percentile; body mass index=18.2 kg / m 2 ).", "He was obese with normal stature ( height=170 cm, z -score=-0.8, 21st percentile; weight=110 kg, z -score=+2.4, 99th percentile; BMI=38.1 kg / m 2 )" ]

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[ "no hirsutism" ]

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[ "17 years of age", "age of 15 and 11 months" ]

[ "4 years of age ,", "3 - year - old" ]

[ "If p. R124C is pathogenic , the most likely phenotype due to compound heterozygosity for p. R124C and a large deletion would be NC CAH", "a diagnosis of NC CAH was confirmed" ]

[ "replacement doses of hydrocortisone and fludrocortisone" ]

[ "height 149.0 cm, weight 39.2 kg, BMI 17.7 kg / m 2" ]

[ "no history of neonatal jaundice or chronic infantile diarrhea" ]

[ "The patient was a 50 - year - old Japanese woman from non - consanguineous parents. She has no siblings but had a child. There was no apparent family history ( parents, child and parent ’s siblings ) of neurological disorders, cardiovascular diseases or any lipid storage diseases inducing xanthomas, including CTX. She had no history of neonatal jaundice or chronic infantile diarrhea. She had been diagnosed with idiopathic epilepsy and medicated from 7 to 10 years of age. Thereafter, she had no remarkable medical developments until middle age. She insidiously developed painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age" ]

[ "did not have dementia based on the Revised Hasegawa Dementia Scale ( HSD - R; 26/30 ), Mini - Mental State Examination ( MMSE; 27/30 ), and Frontal Assessment Battery ( FAB; 16/18 ) scores. On a neurological examination, her gait appeared somewhat spastic, and all of her deep tendon reflexes were mildly enhanced bilaterally with positive Babinski and Chaddock reflexes, indicating impairment in the bilateral pyramidal tracts. There were no neurological findings suggesting cerebellar impairment", "T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) MRI of the brain showed bilateral low - intensity areas in the dentate nuclei and high - intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high - intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable.", "idiopathic epilepsy" ]

[ "no elevation in the levels of serum cholesterol or triglycerides or deficiencies in apolipoproteins or thyroid hormones", "The primary bile acids were extremely low in the serum and urine when measured by both high - performance liquid chromatography ( HPLC ) and gas chromatography / mass spectrometer ( GC / MS ). The urinary levels of bile alcohols, especially 5β - cholestane-3α,7α,12α,24,25 - pentol, were markedly elevated. Norcholic acid, which is mainly derived from 5β - cholestane-3α,7α,12α,23,25 - pentol, was highly elevated and accounted for 78.4 % of all bile acids in the urine. The serum level of cholestanol was extremely elevated, while those of sitosterol and campesterol were not elevated", "T2 - weighted and fluid - attenuated inversion recovery ( FLAIR ) MRI of the brain showed bilateral low - intensity areas in the dentate nuclei and high - intensity areas in the peripheral white matter the cerebellum ( Fig. 1C ). We also found bilateral high - intensity areas along the pyramidal tracts from the pons to the cerebral crus. Brain atrophy was not remarkable", "Ultrasound of the carotid arteries showed a slightly thickened intima - media complex at the left common carotid artery ( maximum intima - media thickness, 1.2 mm", "However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities", "dual - energy X - ray absorptiometry, which showed a bone density of 61 % and 75 % the young - adult - mean in the lumbar vertebra and femoral neck, respectively.", "T1- and T2 - weighted magnetic resonance imaging ( MRI ) revealed low - intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas" ]

[ "Ultrasound of the carotid arteries showed a slightly thickened intima - media complex at the left common carotid artery ( maximum intima - media thickness, 1.2 mm ). However, there was no evidence of cardiovascular disease on electrocardiogram, echocardiography and MR angiography of the brain and lower extremities" ]

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[ "xanthomas on the bilateral Achilles tendons ( Fig. 1B ) and right triceps muscle", "osteoporosis as determined by dual - energy X - ray absorptiometry, which showed a bone density of 61 % and 75 % the young - adult - mean in the lumbar vertebra and femoral neck, respectively", "painless tendon thickness of the bilateral Achilles tendons and right triceps muscle at 47 years of age. The gradual enlargement of the Achilles tendons caused gait disturbance when she was 49 years of age. T1- and T2 - weighted magnetic resonance imaging ( MRI ) revealed low - intensity lesions in the thickened bilateral Achilles tendons ( Fig. 1A ) and right triceps muscle, suggestive of xanthomas." ]

[ "age - appropriate slight cataracts in the bilateral eyes" ]

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[ "no history of neonatal jaundice" ]

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[ "50 - year - old" ]

[ "7 to 10 years of age" ]

[ "the patient was diagnosed with CTX" ]

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[ "poor feeding by breast and bottle" ]

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[ "hypotonic, irritable, and demonstrated poor feeding by breast and bottle", "in utero hiccups", "seizure - like activity", "seizures since birth", "MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N - acetylaspartate ( NAA ) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1 - weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules ( white arrows ). Fig. 1 –. Fig. 2 Axial T2 - weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter ( white arrow ). There is overall low parenchymal volume with prominence of the extra - axial spaces ( black arrow ). Fig. 2 –. Fig. 3 Sagittal T1 - weighted images reveal low parenchymal volume of the superior folia with prominence of the extra - axial spaces ( white arrow ). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N - acetyl aspartate peak.", "seizures requiring prolonged video electroencephalogram ( EEG ) monitoring", "CSF analysis yielded an acellular CSF with normal protein and glucose", "excessive hiccupping, episodes of extensor spasms, and multifocal seizures", "follow - up study of the patient 's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside" ]

[ "MRI showed myelination confined to the brainstem, central cerebellum, and posterior limbs of the internal capsule ( Fig. 1 ). There was T2 hyperintensity of the white matter ( Fig. 2 ) and superior vermian volume loss ( Fig. 3 ). The corpus callosum was unmyelinated. MRI spectroscopy revealed a low N - acetylaspartate ( NAA ) peak with no lactate peak ( Fig. 4 ). Fig. 1 Axial T1 - weighted images of the brain acquired at 3.0 T demonstrate myelination limited to the posterior limbs of the bilateral posterior internal capsules ( white arrows ). Fig. 1 –. Fig. 2 Axial T2 - weighted images of the brain acquired at 3.0 T show increased T2 signal in the periventricular white matter ( white arrow ). There is overall low parenchymal volume with prominence of the extra - axial spaces ( black arrow ). Fig. 2 –. Fig. 3 Sagittal T1 - weighted images reveal low parenchymal volume of the superior folia with prominence of the extra - axial spaces ( white arrow ). The corpus callosum is unmyelinated. Fig. 3 –. Fig. 4 Magnetic resonance spectroscopy performed at TE = 144 ms with a voxel placed in the right posterior parietal white matter demonstrates a dominant choline peak and a diminished N - acetyl aspartate peak.", "CSF analysis yielded an acellular CSF with normal protein and glucose", "follow - up study of the patient 's CSF was found to demonstrate abnormally high concentrations of succinyladenosine and succinylaminoimidazole carboxamide riboside" ]

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[ "born at term by an uncomplicated pregnancy. The patient was hypotonic, irritable, and demonstrated poor feeding by breast and bottle in the first week of life. He had a history of in utero hiccups, which persisted as a neonate" ]

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[ "age of 3 months" ]

[ "in utero" ]

[ "The elevation of these 2 compounds confirmed the diagnosis of adenylosuccinate lyase deficiency ." ]

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[ "This patient was a 4 - year old girl, second child of related parents, delivered by cesarean section without any insult. This child developed wrist swelling at 6 months of age. Swelling of other joints were gradually added", "Reports of head drop attacks were found in the history", "This patient was a 4 year - old girl, first child of a non - related couple, delivered by NVD who was term on birth. The patient developed swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles", "admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old", "This patient was a 9 - month old boy, the first child of related parents who was delivered by NVD without any insult. Rheumatoid arthritis history was positive for patient ’s father. The patient was presented to the clinic at 9 months of age with one month history of left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands" ]

[ "head drop attacks", "deep tendon reflexes were diminished or absent. Although cognitive function of this patient was normal, motor and speech development was delayed. Two years later, development of seizure and tremor was reported. Tremor was evident in all limbs on physical examination", "development of neurologic involvements", "with neurological deficit", "delayed motor development" ]

[ "Laboratory serologic tests were normal. Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints which all were suggestive of advanced juvenile idiopathic arthritis ( JIA ). Chest X - ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia", "ASAH1 gene analysis – gene related to Farber syndrome- revealed a homozygous variant which confirmed the presence of Farber disease in this patient. This variant was a novel mutation in exon 8 of ASAH1 gene ( c.553T > C p. Trp185Arg )", "In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen", "Histopathologic examination reported collection of collagen bundles and foamy macrophages", "On radiography, osteopenia was evident ( bone age equal to 9 months at the age of 18 months ). CXR visualized bilateral perihilar opacities and hyperinflation in both lungs. In kidney, contrast opacity resembling kidney stone was seen. HPLC was normal." ]

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[ "Chest X - ray also showed alveolar opacities with air bronchogram in the upper lobe of right lung which were in favor of pneumonia", "Bronchoscopy showed a circular contraction in subglottic region of larynx", "wheezing", "admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old.", "respiratory distress", "bilateral perihilar opacities and hyperinflation in both lungs", "Laryngeal nodules led to severe respiratory distress which his life ended" ]

[ "wrist swelling", "Swelling of other joints were gradually added", "swelling and limitation in range of motion was detected in PIP, MCP, wrist, elbow and shoulder joints of upper limbs and PIP, MTP, tarsal joints and ankle in lower limbs. Multiple firm subcutaneous nodules were found on joints – mainly on extensor surfaces- which led to deformation of joint, tenderness and inability to walk. Contracture in joints was evident in physical examination", "Radiography of both hands showed reduction in density of bones, swelling of both wrists, deformity of wrist bones, marginal erosion of wrist bones and distal phalanges in PIP and DIP joints", "swelling of joints at 7 months of age. Particularly in PIP and MCP joints, wrists and ankles", "multiple subcutaneous nodules on head, hands and chest", "Limitation in knee ’s range of motion was severe leading to difficulty in walking", "three relatively soft masses were found within lumbar to coccygeal regions of the spine with diameters of up to 5 centimeters", "Muscular atrophy of all four limbs and gluteal region was evident", "Joints ’ examination showed nodules and range of motion limitation in both elbows, shoulders, MCPs, PIPs and DIPs in upper limbs. In lower limbs, knees and ankles were affected with contracture, nodules and range of motion limitation. In radiography, bilateral destruction of proximal humerus and severe osteopenia were seen", "development of multiple percutaneous nodules", "Histopathologic examination reported collection of collagen bundles and foamy macrophages", "Subcutaneous nodules increased gradually", "left wrist swelling and tenderness. Within one week prior to the presentation, swelling had extended to the dorsal surfaces of the hands", "lower limbs were normal but in upper limbs, limitations in flexion and extension of wrist and swelling of fingers were noted", "multiple subcutaneous nodules in wrists and ankles", "osteopenia was evident ( bone age equal to 9 months at the age of 18 months" ]

[ "Progressive hoarseness was present", "Progressive hoarseness was also present. Extensive mucosal lesions were detected in the oral cavity", "nasal swelling", "progression of hoarseness", "admitted 4 times due to respiratory distress. Finally she died from respiratory failure in one episode at 4 years old", "Hoarseness had developed 6 months earlier", "respiratory distress and hoarseness", "large cysts on vocal cords were seen", "Laryngeal nodules led to severe respiratory distress which his life ended" ]

[ "Cutaneous lesions were also seen on abdomen", "appearance of cutaneous lesions on the body" ]

[ "delivered by cesarean section without any insult", "delivered by NVD who was term on birth", "delivered by NVD without any insult" ]

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[ "4 - year old", "4 year - old", "9 - month old" ]

[ "6 months of age", "7 months of age" ]

[ "confirmed the presence of Farber disease in this patient" ]

[ "Bone marrow transplantation was suggested as a treatment strategy for the patient" ]

[ "His heart rate was 120 beats per minute and his blood pressure was 100/65 mmHg. His weight and height were 12.8 kg ( 1.5 SDS ) and 86 cm ( 2 SDS ), respectively", "his body weight and length were 16.7 kg ( 0.5 SDS ) and 99.7 cm ( 1.5 SDS ), respectively" ]

[ "imperforate anus", "tracheoesophageal fistula was not suspected clinically", "anal atresia", "abdomen was distended and discolored", "bowel necrosis", "peritonitis", "peritonitis", "occasional nausea and vomiting" ]

[ "A male child was born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score ) and 52.5 cm ( z -score, +1.4 SDS ), respectively. There was no family history of consanguineous marriages. The patient was born with an imperforate anus and a colostomy was performed the day after birth", "At the age of 3 months, the patient was admitted to the hospital for colostomy takedown, anorectoplasty, and endoscopic dextranomer / hyaluronic acid copolymer injection for VUR", "Bowel resection with colostomy and jejunostomy was performed 3 times, which resulted in short - bowel syndrome", "At the age of 7 months, a takedown of the colostomy and jejunostomy was performed", "At 17 months of age, the patient had an episode of sepsis and peritonitis secondary to Acinetobacter baumannii infection and an exploratory laparotomy was performed to check for bowel necrosis" ]

[ "He was able to ascend stairs with the support of a hand grasp. He could stack 3 cubes, eat without assistance, and pronounce 10 words, meaning that the patient ’s developmental status was normal for his age", "normal growth and development" ]

[ "echocardiography revealed a patent ductus arteriosus", "Bilateral grade 3 vesicoureteral reflux ( VUR ) was revealed via voiding cystourethrography. Spine ultrasound revealed no vertebral anomalies, and tracheoesophageal fistula was not suspected clinically", "Laboratory test results, including electrolyte levels, were normal. Neonatal screening tests for metabolic disease were also normal, including the 17 - alpha - hydroxyprogesterone level. Chromosome analysis revealed a 46, XY karyotype.", "Laboratory investigations revealed a slightly decreased sodium level ( 132 mmol / L ) but normal potassium ( 4.8 mEq / L ) and glucose ( 86 mg / dL ) levels; complete blood count, blood gas profile, hepatic and renal function, thyroid function test and sex hormone levels were obtained. Decreased cortisol ( 1.0 μg / dL ) and markedly elevated adrenocorticotropic hormone ( ACTH ) ( 16,064 pg / mL ) levels were noted. The patient 's cortisol levels did not respond to stimulation with ACTH ( 125 μg ) ( Table 1 ). Meanwhile, he presented a normal 17 - hydroxyprogesterone level ( 0.42 ng / mL ). Plasma renin activity and aldosterone levels were 7.28 ng / mL / hr ( normal range, 1.0–6.5 ng / mL / hr ) and 0.1 ng / dL ( normal range, 3–35 ng / dL ), respectively", "The abdominal ultrasound revealed no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation, or bowel wall thickening", "no pathogenic variants were detected in CYP11A1 genes. The exome - sequencing results revealed compound heterozygous mutations for c.653C > T and c.661G > A ( p. Gly221Ser ) in exon 6 of the STAR gene. Sanger sequencing confirmed the presence of these variants and each of the same heterozygous variant was found in his father and mother, respectively", "Laboratory tests revealed normal levels of cortisol ( 4.6 μg / dL ), sodium ( 139 mmol / L ), potassium ( 4.9 mEq / L ), glucose ( 70 mg / dL ), and ACTH ( 53.6 pg / mL )" ]

[ "A grade 2 systolic murmur was heard in the left upper sternal border and echocardiography revealed a patent ductus arteriosus", "hypotensive" ]

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[ "normal male genitalia, with both testes palpable", "Bilateral grade 3 vesicoureteral reflux ( VUR ) was revealed via voiding cystourethrography", "renal anomalies", "normal male genitalia", "slightly decreased sodium level ( 132 mmol / L ) but normal potassium ( 4.8 mEq / L )", "no abnormalities, such as adrenal enlargement, hydronephrosis, distal ureter dilatation" ]

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[ "postaxial polydactyly of the left foot", "Spine ultrasound revealed no vertebral anomalies", "limb abnormalities", "postaxial polydactyly of the left foot" ]

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[ "slight bronzing of the patient ’s skin after repeated surgeries", "generalized hyperpigmentation", "child 's hyperpigmentation was markedly exacerbated after exploratory laparotomy for the episode of peritonitis with sepsis", "hyperpigmentation", "generalized hyperpigmentation", "generalized hyperpigmentation had improved" ]

[ "born at a gestational age of 39 weeks with no history of antenatal or perinatal problems. Apgar scores were 9 points at one minute and 10 points at 5 minutes. His birth weight and height were 3,800 g ( z -score, +1 standard deviation score ) and 52.5 cm ( z -score, +1.4 SDS ), respectively" ]

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[ "This variant has been previously reported in association with CLAH ." ]

[ "Hydrocortisone ( 7.8 mg / m 2 /day ) and fludrocortisone ( 50 μg / day ) were started as therapy for primary adrenal insufficiency . The dose of hydrocortisone was gradually increased until the age of 24 months for sufficient ACTH suppression and levels of ACTH and cortisol were subsequently decreased to the optimal range" ]

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[ "chronic diarrhea", "remission of diarrhea", "chronic diarrhea", "Three months later, diarrhea was disappeared", "diarrhea recurred" ]

[ "We report a 38 - year old woman who presented with chronic diarrhea and progressive spastic paraparesis in her twenties", "chronic diarrhea, scoliosis and bilateral cataract surgery at age 25" ]

[ "progressive spastic paraparesis in her twenties.", "the patient developed psychosis and an severe ataxospastic gait.", "All patients presented pyramidal signs and 48 % had dorsal column signs", "A 38 - year - old woman presented with progressive muscle stiffness, calf cramps and urinary frequency appeared in her twenties", "Neurological examination revealed spastic paraparesis with pyramidal signs more prominent on the left lower extremity and flat feet. A neurocognitive study demonstrated severe anterograde verbal memory difficulties and minor executive dysfunction. Electroneuromyography ( ENMG ) was normal.", "Neurologic evaluation showed a severe ataxospastic gait with knee recurvatum ( additional files : video ). ENMG was normal." ]

[ "Brain magnetic resonance imaging ( MRI ) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX.", "Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts.", "Brain MRI showed subtle symmetric, bilateral hyperintense T2 ground - glass appearance of the deep white matter, possible symmetric T2 hyperintensity of the cerebellar dentate nuclei and two small ischemic infarct sequelae of the right cerebellar hemisphere ( Fig. 2 ). Spinal MRI was normal.", "Cholestanol was increased to 64 μmol / L ( 3.3–12.5 μmol / L )", "Genetic analysis found two monoallelic mutations in the gene CYP27A1 : a missense mutation ( c.1183C > T; p. Arg395Cys ) in exon 6 and a splicing mutation ( c.1184 + 1 G > A ) in intron 6", "Brain and spinal cord MRI performed in 2008 ( a, b, e ) and 2019 ( c, d, f, g ). Axial plane T2 weighted images ( a - d ) at the level of the dentate nuclei and periventricular white matter showing stable minimal increased signal in the dentate nuclei ( arrowheads ) and questionable slightly abnormal periventricular white matter T2 hyperintensity ( “ ground - glass appearance ” ). The rest of brain MRI was unremarkable except for two small old infarcts in the right cerebellar hemisphere ( one lesion shown in a and b * ). Spinal cord MRI from 2008 ( e ) was unremarkable, though no axial plane images were performed. Spinal cord MRI in 2019 revealed subtle longitudinal high signal ( white arrow - heads ) of the posterior columns at the cervico - dorsal junction and middle dorsal region on sagittal T2 - weighted images ( f ). Axial T2 - weighted images confirmed bilateral, symmetric signal abnormalities corresponding to the gracilis tracts ( g, black arrowhead ) and the lateral cortico - spinal tracts ( g, white arrows ) at different cervical and dorsal levels, without spinal cord atrophy or contrast material ( gadolinium ) uptake.", "Brain MRI was unchanged. Spinal MRI revealed extensive linear T2 weighted hyperintensities appearing bilaterally in lateral corticospinal and gracile tracts", "normal cholestanol levels ( 6.18 μmol / L; normal range 3.3–12.5 μmol / L" ]

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[ "urinary frequency" ]

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[ "progressive muscle stiffness, calf cramps", "scoliosis", "did not found any tendinous xanthomas" ]

[ "bilateral cataract" ]

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[ "38 - year old" ]

[ "her twenties", "her twenties" ]

[ "CYP27A1 gene sequencing confirmed the diagnosis of CTX .", "confirmed CTX diagnosis ." ]

[ "Chenodeoxycholic acid ( CDCA ) treatment was introduced with remission of diarrhea", "Disease improvement or stabilization with chenodeoxycholic acid was observed in 69 % of patients", "A treatment with 750 mg / d chenodeoxycholic acid ( CDCA ) and 20 mg / d simvastatine was introduced" ]

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[ "recurrent abdominal pain and vomiting", "abdominal pain", "multiple episodes of vomiting", "no sign of perianal diseases", "recurrent vomiting" ]

[ "An 8 - year - old girl of non - consanguineous parents from southern China with history of recurrent abdominal pain and vomiting since 4 years of age presented to the gastroenterology department" ]

[ "muscle weakness during attacks." ]

[ "Inflammatory markers, including C - reactive protein and erythrocyte sedimentation rate were within normal limits. Other laboratory investigations showed a lactate of 2.9 mmol / L, pH of 7.311, serum free fatty acid of 2.161 mmol / L.", "serum tandem mass spectrometry was performed, and showed C10 of 1.29 µM, C8 of 0.57 µM, C5 / C3 of 0.362 µM.", "Abdominal computed tomography without contrast showed hepatic lipomatosis", "Trios exome sequencing showed that compound heterozygous mutations of c. + were identified in ETFDH, which was confirmed by Sanger sequencing" ]

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[ "8 - year - old" ]

[ "4 years of age" ]

[ "This patient was diagnosed with late - onset MADD" ]

[ "treated with riboflavin with a dosage of 100 mg / day" ]

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[ "angioid streaks, atrophic retinal break of the right eye, angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease, vitreous degeneration, and bilateral posterior vitreous detachment" ]

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[ "OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50 % at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross - section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50 % of total attenuation at 0.3 mm below the skin surface and near - complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line" ]

[ "angina pectoris, myocardial infarction, peripheral artery disease, coronary artery disease" ]

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[ "angioid streaks, atrophic retinal break of the right eye,", "vitreous degeneration, and bilateral posterior vitreous detachment" ]

[ "yellowish skin papules coalescing into plaques on the lateral neck with skin laxity of the axilla ( Fig 1 ), face, neck, and groin.", "lax and redundant skin", "OCT imaging of the lax axilla skin displayed large areas of hyporeflective, homogeneous areas of attenuation, or signal loss, in the mid dermis ( Fig 3 ). In contrast to normal skin, which attenuates the image at about 0.7 to 0.9 mm, the depth of the PXE image exhibits relative superficial attenuation of 50 % at 0.3 mm and near complete attenuation at a depth of about 0.53 mm. The observed changes may be associated with the noted abundance of elastin at and above this level on histology. Fig 3 OCT cross - section of PXE shows homogenous areas of premature signal loss ( yellow, dotted circle ), with 50 % of total attenuation at 0.3 mm below the skin surface and near - complete attenuation at about 0.53 mm. The approximate depth of the MPM image at 30 μm below the DEJ is marked by the red line, and an approximation of the maximum depth MPM can penetrate is marked by the blue line." ]

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[ "65 - year - old" ]

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[ "long - standing , biopsy - proven diagnosis of PXE" ]

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[ "irregular bowel movements", "loose stools", "early onset of frequent diarrhea" ]

[ "A woman in her 40s, who had 2 family members with CTX, struggled with irregular bowel movements from an early age. She developed cataracts at the age of 11 years and was diagnosed with CTX at age 27", "A woman in her 50s, who has 2 family members formally diagnosed with CTX, had loose stools from childhood. She was diagnosed with cataracts at the age of 20 years and with CTX at 38 years", "A woman in her 30s, with no reported family history of CTX, first experienced symptoms with an early onset of frequent diarrhea in infancy. She developed cataracts by the age of 6 years", "Tendon xanthomas required surgical debulking by the age of 17 years" ]

[ "cerebellar lesions", "patient did not have neurologic deficits", "Significant neurologic involvement developed in the patient, which progressively led to her becoming nonambulatory and wheelchair - bound", "severe cognitive decline", "magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus", "she has not clinically expressed any neurologic motor deficits", "significant cognitive delay" ]

[ "most recent imaging showed cerebellar lesions", "magnetic resonance imaging of the brain showed a mild increased T2 signal within the dentate nucleus" ]

[ "no known cardiovascular involvement", "no known cardiovascular disease", "no known cardiovascular disease" ]

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[ "tendon xanthomas on the fingers and toes, which required debulking, as well as plantar and Achilles xanthomas. She reported no new xanthomas and no changes in the existing xanthomas over 10 years", "acquired xanthomas of the Achilles, knee, and elbow. Her existing xanthomas have remained stable, with no new xanthomas", "Tendon xanthomas", "xanthomas of the Achilles, elbow, and plantar foot and extensor tendons of the fingers and toes. She reported minimal increases in the left Achilles xanthoma over 8 years, with no new xanthomas" ]

[ "cataracts", "cataracts", "visual impairment", "cataracts" ]

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[ "her 40s", "in her 50s", "her 30s" ]

[ "early age", "childhood", "infancy" ]

[ "diagnosed with CTX at age 27", "CTX at 38 years , which was confirmed by genetic testing .", "At the age of 14 years , she was formally diagnosed with CTX , which was confirmed by genetic testing ." ]

[ "prompt initiation of chenodiol therapy . She has been on chenodiol consistently since the diagnosis at age 27 .", "She started chenodiol at the time of the diagnosis", "Chenodiol ( chenodeoxycholic acid ) therapy was initiated at diagnosis , and she has remained on chenodiol since that time" ]

[ "SPO 2 86 %", "130 bpm", "blood pressure 80/59 mmHg" ]

[ "abdominal pain", "recurring abdominal pain and bloating ( almost once per month )", "incomplete intestinal obstruction", "abdominal pain spontaneously disappeared", "abdominal pain and constipation returned" ]

[ "A 37 - year - old woman presented to the surgical unit of a general teaching hospital with abdominal pain that she experienced while walking to the hospital ( May 2019 ). Her symptoms had started 4 months previously ( January 2019 ). The initial symptoms included recurring abdominal pain and bloating ( almost once per month ). During this period, the patient visited her local clinic several times, without obtaining a clear diagnosis", "She had a history of a cesarean section in 2013, and no other notable medical history or family history of disease", "Targeted mutation analysis was then performed in her two children, but neither of them carried the disease - causing gene" ]

[ "muscle weakness, and a disorder of consciousness", "patient ’s awareness gradually recovered", "Muscle power of the limbs was 0/5 proximally and 2/5 distally. Furthermore, sensation and cranial nerve examinations were normal", "Cranial computed tomography ( CT ) and abdominal CT did not indicate any abnormalities", "The initial cerebrospinal fluid ( CSF ) examination was within the normal range, and anti - ganglioside antibodies, such as GM1 and GD1a, were negative", "electromyography findings showed unspecific peripheral nerve damage", "changes in her neurological examination. Her overall weakness worsened, with muscle power of 0/5 ( absolutely no movement ) in all four limbs. Furthermore, a cranial nerve examination showed new nasal and labial asymmetry, and her eyelids were unable to close", "Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation", "peripheral neuropathy did not markedly improve", "poor muscle strength in her limbs", "her overall muscle power had gradually improved to grade 3/5, and she was able to walk with the aid of a rehabilitation walking assistance vehicle", "severe neurological sequelae" ]

[ "an abdominal flat plate X - ray showed incomplete intestinal obstruction", "Urgent arterial blood gas analysis on ICU admission indicated severe hypoxemia and respiratory acidosis ( pH : 7.153, PO 2 : 66 mmHg, PCO 2 : 50.2 mmHg, and PO 2 /FiO 2 : 110 mmHg );", "Cranial computed tomography ( CT ) and abdominal CT did not indicate any abnormalities ( Figure 1b ), although the chest CT showed patchy exudation of the lower lungs, which did not explain the patient ’s respiratory failure. Bedside ultrasound revealed that diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm", "Blood tests showed that serum creatinine was elevated at 350.5 µmol / L ( normal range : 44–133 µmol / L ), and urea nitrogen was elevated at 22.23 mmol / L ( normal range : 2.9–7.5 mmol / L )", "The initial cerebrospinal fluid ( CSF ) examination was within the normal range, and anti - ganglioside antibodies, such as GM1 and GD1a, were negative", "Abdominal CT at this time showed extensive colonic expansion ( Figure 1c ). Another CSF examination was performed, but the results remained normal, with no cytoalbuminologic dissociation.", "genetic analysis, which identified a missense mutation : c.541C > T, encoding p. Gln181 in the HMBS gene" ]

[ "uncorrectable hypoxemia ( SPO 2 86 % ), tachycardia ( 130 bpm ), and hypotension ( blood pressure 80/59 mmHg )" ]

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[ "serum creatinine was elevated at 350.5 µmol / L ( normal range : 44–133 µmol / L ), and urea nitrogen was elevated at 22.23 mmol / L ( normal range : 2.9–7.5 mmol / L )", "color of the patient ’s urine turned visibly reddish on exposure to sunlight", "urine returned to a normal color" ]

[ "dyspnea,", "uncorrectable hypoxemia ( SPO 2 86 % )", "severe hypoxemia and respiratory acidosis", "stubborn respiratory failure", "patient was unable to be removed from the ventilator", "chest CT showed patchy exudation of the lower lungs", "diaphragm displacement during spontaneous breathing mode was 5.4 mm, whereas normal displacement is considered to be greater than 10 mm" ]

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[ "37 - year - old" ]

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[ ". A diagnosis of AIP was finally confirmed by genetic analysis" ]

[ "Because heme arginate is not available in mainland China , the patient was treated with intravenous glucose infusion ( 50 % ) ." ]

[ "Increased leukocyte count, neutrophil ratio", "T ≤ 38.2 ° C )" ]

[ "eating difficulty", "Chronic diarrhea was absent" ]

[ "A 47 - year - old male was admitted to our institution with a history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework. ', ' Personal and family history ' : ' The proband is the 4 th child of 5 in a non - consanguineous Chinese family. His family history was negative for symptoms related to neurological disorders. He was divorced twice and had no children, and did not have a history of smoking or drinking. The proband ’s parents had died and his mother had a history of uremia. All of his four sisters are healthy", "we described a 47 - year - old patient displaying psychiatric and behavioral disturbances, cognitive decline, a history of renal calculus, bilateral xanthomas of the Achilles tendon and tibial tubercles, peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI", "Three months ago, he underwent an operation for renal calculus, after which he showed progressive delusion ( he believed unreasonably that he had a serious disease and was going to die ), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence, fever ( T ≤ 38.2 ° C ) and severe weight loss. Chronic diarrhea was absent." ]

[ "history of intellectual disability for more than 30 years and behavioral abnormalities for the past 3 mo. He had a poor academic performance, having dropped out after completing elementary school. The patient could talk with others in daily life, but he was unable to do housework", "psychiatric signs", "Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy", "poor mental state", "Neurological examination indicated cervical rigidity and Kernig sign. Deep tendon reflexes and limb muscle strength were normal. Babinski sign was negative", "psychiatric and behavioral disturbances, cognitive decline", "peripheral neuropathy, high signal intensity in the WM and mild cerebral atrophy on brain MRI.", "The electroencephalogram ( EEG ) showed increased slow activities than normal and electrophysiological examination found mixed sensorimotor neuropathy of the upper and lower limbs. Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy", "Cerebrospinal fluid protein was mildly elevated : 680.4 mg / L ( normal range : 150 - 400 mg / L", "he showed progressive delusion ( he believed unreasonably that he had a serious disease and was going to die ), combined with slow response and speech reduction. At 1 wk before admission, he was unable to answer questions and developed an eating difficulty, incontinence," ]

[ "There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging ( MRI ) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene ( c.435G > T, c.1263 + 1G > A )", "The main brain MRI abnormalities include supratentorial and infratentorial atrophy, as well as T2W / FLAIR ( fluid - attenuated inversion recovery ) hyperintensity involving the subcortical, periventricular and cerebellar WM and the brainstem. Bilateral hyperintensity of the dentate nuclei ( DN ) and surrounding WM on T2 and FLAIR sequences is considered a representative radiological feature of CTX", "A 6 - year MR follow - up study revealed that cerebellar hyperintensity in T1 - weighted and FLAIR images tend to be replaced by hypointense areas, suggesting vacuolation.", "high signal intensity in the WM and mild cerebral atrophy on brain MRI. The diagnosis was confirmed by compound heterozygous mutations in exon 2 ( c.435G > T, p. Gly145Gly ) and intron 7 ( c.1263 + 1G > A ) of the CYP27A1 gene.", "X - ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally ( Figure 2E ). Sagittal and axial magnetic resonance imaging ( MRI ) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon ( consisting of low signal intensity on both T1- and T2 - weighted images ), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon", "Cerebral MRI suggested white matter ( WM ) demyelination and slight cerebral atrophy ( Figure 2 G and H ). ', ' Laboratory examinations ' : ' The laboratory results ( Table 1 ) were as follows : Increased leukocyte count, neutrophil ratio and high erythrocyte sedimentation rate. There was also a significant increase in concentration of free fatty acid compared to normal range. In contrast, levels of high - density lipoprotein cholesterol were low. Serum cholesterol, glucose, electrolytes, and adrenocorticotropic hormone ( ACTH ) levels were all normal, as were the liver function tests. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position ( Figure 2D ). Cerebrospinal fluid protein was mildly elevated : 680.4 mg / L ( normal range : 150 - 400 mg / L ).", "Targeted sequencing revealed that the proband had compound heterozygous mutations in the CYP27A1 gene" ]

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[ "multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position", "Sediments in the bladder", "history of renal calculus", "Sediments in the bladder", "Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder which could move with body position", "renal calculus", "incontinence" ]

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[ "apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon", "Enlarged Achilles tendons and nodules on the bilateral tibial tubercles were observed", "enlargement of the Achilles tendon, which showed up as low signal intensity on both T1- and T2 - weighted images", "bilateral xanthomas of the Achilles tendon and tibial tubercles", "X - ray of the lower limbs showed soft tissue swelling above the tibial tuberosities bilaterally ( Figure 2E ). Sagittal and axial magnetic resonance imaging ( MRI ) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon ( consisting of low signal intensity on both T1- and T2 - weighted images ), abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon" ]

[ "no evidence of cataract" ]

[ "dark skin", "no evidence of cataract or xanthomas at other sites such as the eyelids" ]

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[ "47 - year - old", "47 - year - old" ]

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[ "CTX", "CTX" ]

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[ "poor feeding and poor weight gain." ]

[ "A 15‐day‐old 46, XY neonate presented with severe adrenal insufficiency", "At 2 years and 5 months, she underwent bilateral gonadectomy" ]

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[ "Laboratory tests revealed severe hyponatremia ( 115 mEq / L ) and hyperkalemia ( 8.6 mEq / L ).", "Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg / mL ( normal 7.2–63.3 pg / mL ). CT showed enlargement of bilateral adrenal glands ( Fig. 1 a ). Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI ( Fig. 1 b ). Since congenital adrenal hyperplasia was strongly suspected, chromosomal genetic testing was performed and revealed a 46,XY karyotype. Sequence analysis of the StAR gene revealed compound heterozygous mutations for p. Q258X and p. D246fs. From these results, lipoid CAH was diagnosed.", "Histopathological findings ' : ' Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids ( Fig. 2 c ). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy ( Fig. 2 d ). Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP / SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5 ). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry ( Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient ( data not shown ). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD" ]

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[ "severe adrenal insufficiency", "Leydig cells were observed both with and without lipid droplets in the testes of this patient. We also demonstrated immunohistochemically that some testosterone‐synthesizing enzymes were maintained in this patient", "severe hyponatremia ( 115 mEq / L ) and hyperkalemia ( 8.6 mEq / L ).", "Not only mineralocorticoids and glucocorticoids, but also adrenal androgens and their metabolic products were barely detectable. On the other hand, concentrations of adrenocorticotropic hormone were extremely high, at 387 pg / mL ( normal 7.2–63.3 pg / mL ). CT showed enlargement of bilateral adrenal glands", "Testosterone‐synthesizing enzymes in the testis of this patient were investigated by immunostaining and Western blotting methods using antibodies reacting with StAR protein, Ad4BP / SF‐1, CYP11A1, CYP17A1, 3β‐HSD, and 17β‐HSD. As control samples, we used biopsy tissues from three individuals with cryptorchidism ( n = 3; mean age, 5 ). All these steroid synthesis‐related proteins were observed in LCs of control samples using immunohistochemistry ( Fig. 3 ). Western blotting analysis showed negative results for StAR protein in the testis of this patient ( data not shown ). LCs both with and without lipid droplets in this patient expressed all the steroid synthesis‐related proteins except StAR, 3β‐HSD, and 17β‐HSD" ]

[ "severe hyponatremia ( 115 mEq / L ) and hyperkalemia ( 8.6 mEq / L ).", "Bilateral gonads were not palpable but were detectable near the internal inguinal rings on ultrasonography and MRI", "Both gonads were identified as normal testes accompanied by vas deferens and epididymis. The testes measured 16 × 10 × 6 mm on the right and 14 × 8 × 8 mm on the left", "Light microscopy showed seminiferous tubules mainly comprising spermatogonia and Sertoli cells, with no spermatocytes or spermatids ( Fig. 2 c ). Two types of LCs were identified, filled with and without lipid droplets in the testicular interstitium. The nuclei of LCs depressed by excessive lipid droplets were more clearly observable under electron microscopy" ]

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[ "Hyperpigmentation suggestive of adrenal insufficiency was noted" ]

[ "born at full term with completely normal female external genitalia. No abnormalities were identified in routine newborn screenings." ]

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[ "15‐day‐old" ]

[ "15‐day‐old" ]

[ "Congenital lipoid adrenal hyperplasia was diagnosed after detection of steroidogenic acute regulatory gene mutations ." ]

[ "hydrocortisone", "adrenocortical hormone replacement therapy" ]

[ "blood in the urine" ]

[ "abdominal pain, constipation", "vomiting", "vomiting, severe intermittent pain in the abdomen", "abdominal pain, constipation,", "vomiting" ]

[ "A gynecologist examined 26 - year - old patient in the 8th week of gestation, due to initial spontaneous abortion, abdominal pain, constipation, muscle weakness, vomiting and dark colour of urine. Previously, she had had a seizure attack at home", "In her personal history she stated to have had a porphyria" ]

[ "seizure attack at home", "reached full orientation and cooperativeness within few minutes. The post - intervention period remained uneventful and the neurological and psychological symptoms returned to the pre - exacerbation status", "patient developed grand mal seizures and expressed agitation. Seizures reached the epileptic status", "state of high psychomotor agitation after the epileptic status", "The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico - subcortical distribution, parieto occipital and frontal," ]

[ "In laboratory findings porphyrin derivatives ( delta aminolevulinic acid 7.76 mg / dU- ( reference range 1.5 - 7.5 ) and porphobilinogen 16.84 mg / dU- ( reference range 0 - 3.4 ) were elevated", "Porphyria markers decreased within the next four weeks", "The brain CT pointed atthe left parietal paramedian hypodense area 16 mm in diameter. The MRI of the brain described the bilateral symmetric lesions of cortico - subcortical distribution, parieto occipital and frontal, which according to MRI characteristics primarily refer to posterior reversible encephalopathy within the metabolic disorder. In laboratory findings, pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia were verified. Biochemical was proven of AIP, high positive variability of total porphyrins ( 700 μg / dU- reference interval < 220 ), uroporphyrin ( 185 mg / dU ), copro - porphyrin ( 515 mg / dU ), delta amino levulinic acid ( 19.50 mg / dU ) and porphobilinogen ( 98 mg / dU ) )" ]

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[ "The first attack in our patient was most probably provoked by taking hormonal contraception", "The last four months the patient was on oral contraceptives ( 0.035 mg ethinyl estradiol and 2.0 mg cyproteronacetat ) due to irregular menstrual cycles", "Her therapy was dydrogesterone." ]

[ "dark colour of urine", "frequent urination, blood in the urine", "irregular menstrual cycles", "pronounced hyponatremia, hypokalemia, hypomagnesemia, and hypocalcaemia", "dark colour of urine" ]

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[ "muscle weakness", "muscle weakness" ]

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[ "8th week of gestation, due to initial spontaneous abortion, abdominal pain", "8th week of gestation, due to initial spontaneous abortion, abdominal pain," ]

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[ "26 - year - old patient", "26 - year - old" ]

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[ "AIP" ]

[ "she was given haem arginate , glucose and symptomatic drugs , and she recovered completely", "she was given haemarginate , glucose" ]

[ "mild anemia and splenomegaly", "normal complete blood count", "enlarged spleen 4 cm below the left costal margin. Blood investigation showed pancytopenia", "normal serum iron profile", "Total white blood cell count ( 4000 - 11,000 / mm 3 ) 1700 / mm 3 3600 / mm 3 4500 / mm 3 Platelets ( 150,000 - 450,000 / mm 3 ) 107,000 / mm 3 150,000 / mm 3 175,000 / mm 3 Hemoglobin ( female : 12.0 - 15.5 g / dL ) 9.4 g / dL 8.7 g / dL 12 g / dL '" ]

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[ "presented at the age of 18 years with photoinduced skin blistering of the face and extremities since her sixth day of life. She had associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose", "She died at the age of 24 from a secondary infection", "A 35 - year - old woman, born to phenotypically normal parents, presented with progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities ( Fig 3 ) and progressive deformities of both hands. She had a history of recurrent keratoconjunctivitis and complications requiring enucleation of her left eye", "enucleation of the left eye", "A 17 - year - old female ( now 37 years old ), born from a nonconsanguineous marriage, presented with a history of spontaneous blistering over photoexposed areas, starting in the first few days of her life. The lesions healed with scarring that led to progressive deformities of her hands, ears, and nose by 18 years of age.", "Three of her 7 siblings were similarly affected. Two of the affected siblings died shortly after birth, and a third, her older sister ( case 2 ), died at the age of 24. Both parents were phenotypically normal." ]

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[ "Laboratory reports revealed a normal complete blood count but an abnormal porphyrin profile", "In case patients 1 and 3, sequencing of the UROS gene, exons 1 to 10 including flanking intronic regions, showed a homozygous transversion of T to G at nucleotide 416 in exon 7 ( c.416T > G ) leading to an L139R protein substitution at the terminal of the β6 protein chain.", "Blood investigation showed pancytopenia, elevated erythrocyte sedimentation rate, positive creatinine - reactive protein, a normal serum iron profile, and an abnormal porphyrin profile", "Urine total porphyrin ( 25 - 144 nmol / L ) 11,986 nmol / L NA 13,269 nmol / L Fecal porphyrin ( 10 - 200 nmol / g ) 5569 nmol / g NA 1797 nmol / g Plasma porphyrin ( < 11.2 nmol / L ) NA NA 1120.5 nmol / L Plasma porphyrin peak 618 nm NA 618 nm Erythrocyte porphyrin ( 0.4 - 1.7 μmol / L ) 35.8 μmol / L NA 26.2 μmol / L Total white blood cell count ( 4000 - 11,000 / mm 3 ) 1700 / mm 3 3600 / mm 3 4500 / mm 3 Platelets ( 150,000 - 450,000 / mm 3 ) 107,000 / mm 3 150,000 / mm 3 175,000 / mm 3 Hemoglobin ( female : 12.0 - 15.5 g / dL ) 9.4 g / dL 8.7 g / dL 12 g / dL ' }" ]

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[ "Wood 's lamp examination revealed pink - red fluorescence of the urine", "red discharge in her diaper" ]

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[ "bilateral extremities showed sclerodermatous contracture and acro - osteolysis", "Acro - osteolysis and contracture of the bilateral hands", "progressive bilateral deformities of the hands", "progressive deformities of both hands", "mutilations of both hands", "progressive deformities of her hands", "disfiguration of the nose, ears, and fingertips bilaterally to the proximal interphalangeal joints" ]

[ "having had photophobia and diminished vision in the right eye", "partial absorption of both ears; and brownish - pink - colored teeth", "Ectropion and bilateral keratoconjunctivitis were apparent", "recurrent keratoconjunctivitis and complications", "microstomia ( Fig 3 ), erythrodontia", "Wood 's lamp examination revealed pink - red fluorescence of the urine and teeth", "redness and matting of both eyes", "deformities of her eyelids, making it difficult to close them fully", "reddish - brown tooth discoloration and disfiguration of the nose, ears", "Eye examination revealed severe ectropion, trichiasis, and scleral melting", "reddish - brownish discoloration of the teeth. B, Severe ectropion, trichiasis, and scleral melting" ]

[ "photoinduced skin blistering of the face and extremities", "associated progressive deformities of her bilateral hands and feet, bilateral ears, and nose", "sclerodermatous changes and hypopigmented and hyperpigmented scars over the face and extremities ( Fig 2, A ); partial absorption of both ears", "Hypertrichosis over the face and arms was present, and the bilateral extremities showed sclerodermatous contracture and acro - osteolysis", "Sclerodermatous changes and hypopigmented and hyperpigmented scars over the face", "progressive bilateral deformities of the hands and photoblistering since birth, with resulting dyspigmentation, scarring, and sclerodermatous changes of the face and distal extremities", "Facial hypertrichosis, microstomia", "mutilations of both hands", "Dyspigmentation, scarring, and sclerodermatous changes over the face", "spontaneous blistering over photoexposed areas", "lesions healed with scarring that led to progressive deformities of her hands, ears, and nose", "thickened skin, hypopigmentation and hyperpigmentation, and scarring at photoexposed sites ( Fig 1, A ); facial hypertrichosis", "Thickened skin with hypopigmentation and hyperpigmentation and scarring over photoexposed sites, facial hypertrichosis" ]

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[ "35 - year - old", "17 - year - old" ]

[ "presented at the age of 18 years", "birth" ]

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[ "The patients were advised to use strict photoprotection" ]

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[ "The proband was born full - term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg / dL." ]

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[ "Laboratory evaluation showed low cortisol at < 0.2 µg / dL ( both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg / dL )", "he developed hyponatremia ( sodium 130 mmol / L ) and hyperkalemia ( potassium 7.2 mmol / L )", "Additional neonatal evaluation included normal newborn screen ( although undetectable 17 - hydroxyprogesterone ), normal pituitary on brain magnetic resonance imaging, normal chromosomal microarray, and 46,XY karyotype. He had an elevated ACTH > 1250 pg / mL ( normal 0 - 46 ), elevated plasma renin activity 193 ng / mL / h ( normal 2 - 37 ), and low aldosterone 3 ng / dL ( normal 6 - 179 ) indicative of primary adrenal insufficiency. Serum 17 - hydroxyprogesterone was also undetectable at < 10 ng / dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU / mL ( normal 0.02 - 7.0 ) and follicle - stimulating hormone 7.9 mIU / mL ( normal 0.16 - 4.1 ), and low total testosterone 5.6 ng / dL ( normal 60 - 400 ) consistent with hypergonadotropic hypogonadism", "Results revealed a heterozygous novel variant in STAR at c.65 - 2A > C", "Targeted variant testing was negative for the variant in both parents, confirming a de novo pathogenic variant in the proband. No other potential pathogenic variants were detected in genes associated with a difference of sex development." ]

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[ "persistent hypoglycemia with blood glucoses of 20 to 30s mg / dL.", "low cortisol at < 0.2 µg / dL ( both at time of hypoglycemia and following 1 µg adrenocorticotropic hormone stimulation test, with normal for these being ≥18 µg / dL ),", "adrenal insufficiency", "hyponatremia ( sodium 130 mmol / L ) and hyperkalemia ( potassium 7.2 mmol / L", "undetectable 17 - hydroxyprogesterone ), normal pituitary on brain magnetic resonance imaging", "He had an elevated ACTH > 1250 pg / mL ( normal 0 - 46 ), elevated plasma renin activity 193 ng / mL / h ( normal 2 - 37 ), and low aldosterone 3 ng / dL ( normal 6 - 179 ) indicative of primary adrenal insufficiency. Serum 17 - hydroxyprogesterone was also undetectable at < 10 ng / dL. At 2 months of age, during the minipuberty of infancy, he had an elevated luteinizing hormone 17.5 mIU / mL ( normal 0.02 - 7.0 ) and follicle - stimulating hormone 7.9 mIU / mL ( normal 0.16 - 4.1 ), and low total testosterone 5.6 ng / dL ( normal 60 - 400 ) consistent with hypergonadotropic hypogonadism." ]

[ "bilateral descended testes and a fused scrotum with a small phallus ( 1.5 cm × 0.08 cm )", "hyponatremia ( sodium 130 mmol / L ) and hyperkalemia ( potassium 7.2 mmol / L" ]

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[ "born full - term to nonconsanguineous parents by spontaneous vaginal delivery following an uncomplicated gestation. On the day of delivery, he was found to have persistent hypoglycemia with blood glucoses of 20 to 30s mg / dL." ]

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[ "confirming a diagnosis of LCAH ." ]

[ "hydrocortisone", "Fludrocortisone" ]

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[ "An 18 - year - old woman came in with swelling in her ankles and a cognitive decline" ]

[ "cognitive decline", "frequent stumbles and difficulty walking, followed by ataxia", "Spastic paraparesis, rapid deep reflexes, and extensor plantar responses were discovered during a neurological examination. The Romberg test resulted in a positive result with 1 eye closed.", "On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei ( with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits )", "Axial and coronal FLAIR images showing hyperintensities of dendate nuclei ( arrows ) and periventricular white matter" ]

[ "Total cholesterol, LDL, HDL, and triglyceride levels were all within normal limits. Otherwise, the amounts of cholestanol and bile alcohol in the bile and urine were high. An ultrasound of the ankles and knees revealed well - defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons ( Achilles, quadriceps and patellar tendons ( Fig. 1 ). Fig. 1 US of ankle and knee swelling revealing a well - defined, homogenous, hyperechoic mass completely replacing the Achille ( arrow ) and patellar tendons ( star ) Fig 1 The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles. The axial image revealed low signal intensity patches strewn over the muscle, giving it the distinctive speckled look ( Fig. 2 ) Fig. 2 Sagittal proton density image ( A ), T1 - weighted image ( B ), fat suppression on short tau inversion recovery ( STIR ) ( C ), T1 - fat - saturated - weighted image following contrast agent injection ( D ), T1 - weighted image with fat saturation ( E)demonstrating a fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle ( arrows ), with widely spaced tendon fibers interposed with fat ( speckled appearance ) ( star ) Fig 2 On T2 weighted and FLAIR sequences, MRI of the brain revealed hyperintensity of the dentate nuclei ( with a hypo intensity on susceptibility weighted imaging corresponding to calcification deposits ) ( Fig. 3 ). Fig. 3 Axial and coronal FLAIR images showing hyperintensities of dendate nuclei ( arrows ) and periventricular white matter ( stars ) Fig 3 A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes" ]

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[ "swelling in her ankles", "bilateral increasing ankle edema.", "knees swelled", "Over all Achilles, quadriceps, and patellar tendons, the osteo - myo - articular examination revealed bilateral painless and non - fistulized masses", "An ultrasound of the ankles and knees revealed well - defined, homogeneous, hyperechoic masses that had nearly completely replaced the tendons ( Achilles, quadriceps and patellar tendons", "well - defined, homogenous, hyperechoic mass completely replacing the Achille ( arrow ) and patellar tendons ( star )", "The Achilles tendons had a fusiform expansion with a convex anterior border and were isointense to muscle on MRI of the ankles.", "fusiform enlargement of the Achilles tendon, which has a convex anterior border and is isointense to muscle ( arrows ), with widely spaced tendon fibers interposed with fat ( speckled appearance ) (", "A biopsy at the level of Achilles tumefaction showed an aspect of tendinous xanthoma made of fibroblastic tissue remodelled by a dense inflammatory granuloma rich in cholesterol crystals. In contact with these crystals, numerous multinucleated giant cells were observed, associated with numerous foamy histiocytes." ]

[ "sight issues.", "A bilateral thick cataract with impaired vision" ]

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[ "18 - year - old" ]

[ "7 years old" ]

[ "CTX" ]

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[ "presenting dermatosis in the neck with a 3 - month evolution", "severe visual acuity diminution and angioid striae of the retina" ]

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[ "The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed ( Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification", "An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed ( Fig. 2b ). The staining of elastic fibers ( Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside" ]

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[ "severe visual acuity diminution and angioid striae of the retina", "Fundus examination in both eyes revealed classic - appearing angioid streaks with crystalline spots, retinal pigment with epithelial atrophy ( peripapillary ), and choroidal neovascularization", "ocular findings" ]

[ "dermatosis in the neck", "confluent papules, of 2 to 3 mm approximately, discretely hyperpigmented and asymptomatic", "The biopsy showed anfractuous epidermis, with stratum corneum in basket weave, the stratum spinosum thinned with flattening of the interpapillary projections and hyperpigmentation of the cells of the lower third. A perivascular inflammatory infiltrate formed by lymphocytes was observed in the papillary dermis and the superficial reticular dermis. In the middle reticular dermis, short, basophilic, granular, and irregularly shaped fibers were observed ( Fig. 1b ). With staining for elastic fibers, they were shown to be fragmented, and Von Kossa staining evidenced their calcification", "bilateral symmetrical dermatosis was observed, predominantly in folds, characterized by loose skin, soft texture, and plaques consisting of skin - colored papules 3–4 mm in diameter", "An incisional biopsy was taken by punching, with a clinical diagnosis of PXE. In the sections, thin and anfractuous epidermis was observed, with the stratum corneum in basket weave and the stratum spinosum with flattening of the interpapillary projections. In the middle reticular dermis, irregularly arranged short basophilic fibers were observed ( Fig. 2b ). The staining of elastic fibers ( Fig. 2c ) showed that the fragmented debris corresponded to these fibers and Von Kosa staining showed the presence of calcium inside", "characteristic pseudoxanthomatous papules and plaques on the neck or flexural creases, and histopathological changes in lesional skin : calcified elastic fibers in the mid and lower dermis, confirmed by positive calcium stain" ]

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[ "36 years", "59 years" ]

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[ "These clinical and histopathological findings confirmed the diagnosis of pseudoxanthoma", "With the histopathological study and fundus examination findings , the diagnosis of PXE was confirmed this case ." ]

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[ "heart rate of 90 bpm and blood pressure of 160/90 mmHg", "hemoglobin, electrolytes, hepatic transaminases, amylase, thyroid function, protein electrophoresis, and C - reactive protein were normal" ]

[ "Recurrence of abdominal pain, nausea, and vomiting", "proctitis", "intense abdominal pain", "intermittently tender, non - distended abdomen with normal bowel sounds and absent rigidity, rebound, and guarding", "distended colon and fecal impaction", "rectal blood", "proctitis", "abdominal pain and constipation", "severe abdominal pain, nausea, and vomiting", "Epigastric pain", "abdominal pain" ]

[ "Recurrence of abdominal pain, nausea, and vomiting in a kidney transplant patient", "The patient had no known family history of porphyria", "transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephro - pathy", "treated for hypertension since 1994 and developed ischemic heart disease", "a left nephrectomy was performed for a small incidental renal carcinoma", "deceased - donor kidney transplant in 2015", "diabetes mellitus post - transplant" ]

[ "anxiety", "AIP", "mild distress", "anxious mood and low energy level", "agitation and anxiety" ]

[ "His urinary postprandial blood glucose level was 60 mg/24 h ( normal, < 2 mg/24 h", "Plain X - rays of the abdomen showed distended colon and fecal impaction, and ultrasound revealed that the liver, spleen, pancreas, and transplanted kidney were of normal size and consistency and that the site of the left nephrectomy was occupied by intestinal loops. ', ' Laboratory examinations ' : ' Serum levels of hemoglobin, electrolytes, hepatic transaminases, amylase, thyroid function, protein electrophoresis, and C - reactive protein were normal, as was the urine analysis. Renal function was stable with a serum creatinine of 1.2 mg / dL; the urine culture was negative. '", "ultrasound examination demonstrated small echogenic kidneys", "The histopathologic examination of the nephrectomy specimen revealed angiosclerosis and tubulointerstitial fibrosis" ]

[ "hypertension", "hemodynamically stable", "tachycardia and an increase in blood pressure", "thoracic pain", "precordial pain", "for hypertension", "ischemic heart disease" ]

[ "diabetes mellitus which required insulin", "diabetes mellitus" ]

[ "suspected nephroangiosclerosis and chronic interstitial nephro - pathy", "Renal function was stable with a serum creatinine of 1.2 mg / dL; the urine culture was negative", "His renal function gradually deteriorated over the years due to suspected nephroangiosclerosis and chronic interstitial nephropathy", "small echogenic kidneys", "small incidental renal carcinoma", "The histopathologic examination of the nephrectomy specimen revealed angiosclerosis and tubulointerstitial fibrosis" ]

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[ "65 - year - old", "65 - year - old" ]

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[ "He was placed on a high carbohydrate diet ," ]

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[ "A 14 - year - old girl presented in Dermatology outpatient department, with a few skin lesions over face and anterior aspect of her neck for one month ( Fig. 1 ). The lesions measured approximately 2–5 mm in size. A history of pruritis was present", "A history of skin laxity or joint hypermobility was absent", "Family history was not significant" ]

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[ "Hematoxylin and eosin ( H&E ) stained microsections examined from the skin biopsy submitted showed, a prominent granular layer with mild spongiosis and basal layer vacuolization. The papillary dermis was mildly edematous with evidence of mild lymphoplasmacytic infiltrate along with few histiocytes. The mid and lower dermis revealed a prominent zone of chronic inflammatory infiltrate comprising of lymphocytes, histiocytes, and occasional plasma cells. Giant cells were also evident in the mid - dermis. In the middle reticular dermis, deposition of basophilic mucoid material along with haphazardly arranged clumped fragmented elastic fibres were seen. This basophilic mucoid material stained positive for alcian blue, colloidal iron, and Von - Kossa ( Fig. 2 ). The adnexal structures and subcutaneous adipose tissues were essentially unremarkable. Staining for acid - fast bacilli was non - contributory.", "Hematoxylin and Eosin stained section of skin biopsy showed ( a ) upper and mid dermis ( demarcated by black line ) involved with a prominent chronic inflammatory infiltrate, ( b ) Deep basophilic mucoid material in dermis ( demarcated by arrow mark & star mark ) stained positive for alcian blue and, ( c ) colloidal iron and, ( d ) Fragmentation and calcification of dermal elastic fibers is evident on Von Koss stain" ]

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[ "joint hypermobility was absent" ]

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[ "few skin lesions over face and anterior aspect of her neck for one month ( Fig. 1 ). The lesions measured approximately 2–5 mm in size. A history of pruritis was present", "skin laxity or joint hypermobility was absent", "2–5 mm lesions ( milia ) over face", "Hematoxylin and eosin ( H&E ) stained microsections examined from the skin biopsy submitted showed, a prominent granular layer with mild spongiosis and basal layer vacuolization. The papillary dermis was mildly edematous with evidence of mild lymphoplasmacytic infiltrate along with few histiocytes. The mid and lower dermis revealed a prominent zone of chronic inflammatory infiltrate comprising of lymphocytes, histiocytes, and occasional plasma cells. Giant cells were also evident in the mid - dermis. In the middle reticular dermis, deposition of basophilic mucoid material along with haphazardly arranged clumped fragmented elastic fibres were seen. This basophilic mucoid material stained positive for alcian blue, colloidal iron, and Von - Kossa ( Fig. 2 ). The adnexal structures and subcutaneous adipose tissues were essentially unremarkable. Staining for acid - fast bacilli was non - contributory.", "Hematoxylin and Eosin stained section of skin biopsy showed ( a ) upper and mid dermis ( demarcated by black line ) involved with a prominent chronic inflammatory infiltrate, ( b ) Deep basophilic mucoid material in dermis ( demarcated by arrow mark & star mark ) stained positive for alcian blue and, ( c ) colloidal iron and, ( d ) Fragmentation and calcification of dermal elastic fibers is evident on Von Koss stain" ]

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[ "14 - year - old" ]

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[ "Based on characteristic histopathology features , a diagnosis of PXE was offered" ]

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[ "Blood pressure remained normal" ]

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[ "A 24 - year - old woman with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease ( CKD ) was referred for preconception counseling", "There were no overt extra - renal complications apart from mild photophobia", "The infant had normal growth and development at 18 months and a normal leucocyte cystine level." ]

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[ "Cystinosis was confirmed by an elevated leucocyte cystine level in infancy", "Her average prepregnancy urine protein - to - creatinine ratio was 132 mg / mmol, α1 - microglobulin - to - creatinine ratio was 30.7 mg / mmol, and estimated glomerular filtration rate ( eGFR ) was 89 ml per minute per 1.73 m 2", "proteinuria and eGFR increased during pregnancy", "Average leucocyte cystine increased from 0.15 nmol ½ cystine per mg protein to 4 nmol ½ cystine per mg protein" ]

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[ "mild photophobia" ]

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[ "Blood pressure remained normal with no evidence of gestational hypertension or pre - eclampsia", "The pregnancy was complicated by recurrent urinary tract infections ( UTIs ) in the first and second trimesters, and a complicated UTI at 29 weeks with Staphylococcus epidermidis bacteriuria and bacteremia", "She developed spontaneous preterm rupture of membranes at 33 weeks and 1 day gestation, and delivered a male infant who weighed 1886 g via spontaneous vaginal delivery. Apgar scores were 4, 7, and 9 at 1, 5, and 10 minutes", "The postpartum proteinuria stabilized at a level higher than the prepregnancy values, and α1 - microglobulin - to - creatinine ratio and eGFR were stable", "She exclusively breastfed for 4 months and discontinued at 5 months" ]

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[ "24 - year - old" ]

[ "infancy" ]

[ "with infantile nephropathic cystinosis and stage G2A3 chronic kidney disease ( CKD )" ]

[ "Cysteamine was reinitiated immediately after delivery" ]

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[ "A 32 - year - old female ( gravida 4 para 3 ) presented to her obstetrician with her next pregnancy following the birth of a previous female child with classical congenital adrenal hyperplasia ( CAH )", "surfacing of psychological issues for the proband sibling with regards to her external genitalia" ]

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[ "A postnatal follow - up MRI of the patient on day 10 of life showed a total brain volume ( 300.82 cm 3 ) that was below the 5th percentile for age - matched, healthy infants", "The neonate had an elevated serum 17 - OHP of 11,500 ng / dL ( normal range for term newborns within 12 h of birth : ≤460 ng / dL ), androstenedione 4917 ng / dL ( normal range not established for newborns; normal range for infants : 6–78 ng / dL ), and testosterone 279 ng / dL ( normal range of females 1–10 days old : ≤24 ng / dL )" ]

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[ "Prader stage 3, with clitoral width 1 cm, stretched clitoral length 1 cm, and noticeable hyperpigmentation and rugation of the labioscrotal folds", "no concerns for adrenal crisis" ]

[ "Prader stage 3, with clitoral width 1 cm, stretched clitoral length 1 cm, and noticeable hyperpigmentation and rugation of the labioscrotal folds" ]

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[ "hyperpigmentation and rugation of the labioscrotal folds." ]

[ "The estimated fetal age was 15 weeks and 4 days at the time of presentation based on initial sonographic assessments. At 19.42 gestational weeks ( GWs ), ultrasound revealed genitalia that were female - appearing but ambiguous or atypical. A karyotype indicated the fetus was 46,XX with no chromosomal abnormalities. CYP21A2 gene testing of DNA from amniotic fluid showed compound heterozygosity for an R356W mutation on one allele and a 30 - kb deletion on the other allele", "At 29.14 GW, high - resolution prenatal ultrasound ( General Electric, 5 - 9 MHz transducer ) was performed and three serial 2D measurements of the biparietal diameter ( 71.1 mm; 20th percentile ) of the fetus and two serial 2D measurements of the head circumference ( 258.1 mm; 3rd percentile ) were averaged and compared with standard references using the Hadlock growth curves. 2 At 30.57 GW, fetal magnetic resonance imaging ( MRI; Philips 1.5 T ) was performed to better evaluate clinically for other abnormalities as MRI can provide information regarding certain conditions like white matter abnormalities and temporal lobe atrophy that can not be obtained by ultrasound alone. 3 2 - D and 3 - D MRI measurements of fetal brain structures were computed ( Figure 1 ) and shown in Table 1. 2 - D measurements of brain biparietal diameter, occipitofrontal diameter, skull biparietal diameter, and occipitofrontal diameter, and calculated head circumference were recorded. 4 Significant deficits were noted for skull biparietal diameter and occipitofrontal diameter versus age - matched controls ( Figure 2 ). 5, 6 Absolute biparietal diameter measurements were similar for ultrasound and MRI. 3 - D measurements were obtained of the extra - axial cerebrospinal fluid ( CSF ) volume, supratentorial volume, cerebellar volume, cortical plate volume, and total lateral ventricles volume ( Figure 3 ). 4 Total intracranial volume and deep gray matter volume, but not developing white matter, showed deficits versus controls" ]

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[ "fetal age was 15 weeks and 4 days" ]

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[ "prenatal diagnosis of CAH due to 21 - hydroxylase deficiency" ]

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[ "severe abdominal pain, constipation", "severe abdominal pain", "abdominal pain" ]

[ "severe abdominal pain, constipation, and headache, which had started 10 days ago. Within the next few days following admission, the patient developed an attack of generalized tonic - clonic seizure associated with low - grade fever" ]

[ "headache", "an attack of generalized tonic - clonic seizure", "confused in post ictal state. Otherwise, the neurological and general examination was unremarkable", "Urgent brain computed tomography ( CT ) scan showed brain edema", "began to become agitated", "weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic", "Electrophysiological studies were done, which revealed evidence of purely motor axonal polyneuropathy affecting upper and lower limbs with bilateral facial axonal neuropathy ( prolonged first time ( F ) wave latencies with reduced amplitude of compound motor action potentials", "respiratory muscle involvement", "The CSF examination showed cytoalbuminous dissociation", "weakness" ]

[ "Urgent brain computed tomography ( CT ) scan showed brain edema", "abdominopelvic CT scan with contrast was done, which revealed marked distention of large bowel, and no definite air - fluid level or obstructing masses", "The initial results of laboratory investigation revealed marked electrolyte disturbances; sodium level : 108 milliequivalents per liter ( mEq / L ), potassium level : 2.7 mEq / L, total calcium level : 4.9 mg / dl, ionized calcium level : 3.5 mg / dl, magnesium level : 0.7 mEq / L, and phosphorus level : 2.1 mEq / L ( table 1", "urine osmolarity 277mOml / kg, serum osmolality 252 mmol / kg, serum chloride 73 mEq / L, and urinary Calcium / creatinine ratio 1.053", "The CSF examination showed cytoalbuminous dissociation", "Genetic sequencing results showed a heterozygous pathogenic variant in the hydroxymethylbilane synthase ( HMBS ) gene" ]

[ "hemodynamically stable" ]

[ "polyuria, and polydipsia" ]

[ "marked electrolyte disturbances; sodium level : 108 milliequivalents per liter ( mEq / L ), potassium level : 2.7 mEq / L, total calcium level : 4.9 mg / dl, ionized calcium level : 3.5 mg / dl, magnesium level : 0.7 mEq / L, and phosphorus level : 2.1 mEq / L ( table 1", "polyuria, and polydipsia", "renal tubular defect with increased renal loss of electrolyte", "urine osmolarity 277mOml / kg, serum osmolality 252 mmol / kg, serum chloride 73 mEq / L, and urinary Calcium / creatinine ratio 1.053" ]

[ "respiratory muscle involvement" ]

[ "developed generalized muscle pain", "weakness in both lower limbs, right more than left, which was rapidly progressing to involve upper limbs associated with trunk muscle affection till the patient became quadriplegic", "respiratory muscle involvement", "weakness" ]

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[ "13 - year - old" ]

[ "13 - year - old" ]

[ "confirmed the diagnosis of autosomal dominant AIP" ]

[ "The patient received dextrose 25 % and 2 doses of hemin 250 mg once daily for four days , 2 weeks apart followed by another dose after 2 months . There was a marked improvement regarding the weakness , and abdominal pain , and we managed to wean her from mechanical ventilation ." ]

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[ "intermittent abdominal pain accompanied by changes in stool habits", "mild tenderness in the right lower abdomen", "intermittent abdominal pain accompanied by changes in stool habits", "no abdominal distention, nausea, vomiting, constipation, or diarrhea", "mild tenderness only in the right lower abdomen" ]

[ "The patient was a 32 - year - old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms.", "she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital", "Given the patient ’s family history of colon and uterine cancer", "A 32 - year - old female patient was admitted to The First Affiliated Hospital of Air Force Medical University on August 27, 2021, after experiencing intermittent abdominal pain accompanied by changes in stool habits for 3 months. The patient reported no abdominal distention, nausea, vomiting, constipation, or diarrhea. In terms of family medical history, the patient ’s mother had undergone surgery for colon cancer in July 2015 and May 2021, and for cervical cancer in December 2020, and was living without disease recurrence at the time of the patient ’s visit to our hospital", "On the patient ’s maternal side, there was a history of rectal cancer ( the patient ’s grandmother, an uncle, and an aunt ), uterine cancer ( a 29 - year - old female cousin ), rectal cancer with uterine cancer ( two aunts ), and colon polyposis ( a 29 - year - old male cousin )", "Given the patient ’s family history of cancer" ]

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[ "Preoperative abdominal contrast - enhanced computed tomography ( CT ) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery ( SMA ). On the other side, the SMA and superior mesenteric vein ( SMV ) were found to be accompanied like “ X”-shaped variant", "The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon", "No significant abnormalities were found in serum tumor markers", "Biopsy suggested moderately differentiated adenocarcinoma ( Figure 1C ). Abdominal contrast - enhanced computed tomography ( CT ) showed ascending colon cancer with intussusception", "surgery，abdominal contrast - enhanced CT revealed two ICAs deriving from the SMA ( Figure 3A ). The right colic artery ( RCA ) originated from the front of the SMA ( Figure 3B ). The proximal end of the SMA was located on the left side of the SMV, but the distal end of the SMA was always located on the right side of the SMV ( Figure 3A,3C )", "Surgical pathology results suggested that the ascending colon mass was a moderately differentiated adenocarcinoma with locally advanced mucinous adenocarcinoma. The pathological staging was pT3N1aM0 according to the American Joint Committee on Cancer ( AJCC ) Cancer Staging Manual, Eighth Edition ( Figure 4 ). Immunohistochemical results showed positive expression of MSH2 and MSH6 ( Figure 5A,5B ), but negative expression of MLH1 and PMS2 in the patient ’s tumor sample", "the results revealed MLH1 c.885 - 1_893del" ]

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[ "32 - year - old", "32 - year - old" ]

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[ "The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon . Given the patient ’s family history of colon and uterine cancer combined with the results of immunohistochemical staining and next - generation sequencing , we concluded that she had Lynch syndrome ( LS" ]

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[ "On presentation, she was afebrile ( 36.7 ° C ), had a normal heart rate ( 85 beats per minute ), normal respiratory rate ( 16 breaths per minute ), and was normotensive ( 121/80 mmHg )." ]

[ "no bowel movements and diffuse abdominal pain. The abdominal pain was described as a fullness or bloating sensation", "severe nausea and negligible improvement of her abdominal pain", "The abdomen was soft, nondistended, with mild upper abdominal and periumbilical tenderness", "Her appetite improved, but her abdominal pain persisted", "pain remained out of proportion to her physical examination", "abdominal pain and bowel symptoms resolved" ]

[ "A 22 - year - old Hispanic female with a past medical history of dysmenorrhea and recurrent urinary tract infections ( UTIs ), previously diagnosed by her primary care physician, presented with an 8 - day history of no bowel movements and diffuse abdominal pain. The abdominal pain was described as a fullness or bloating sensation. She had tried multiple laxatives for symptom relief. She also reported frequent antibiotic usage, most recently ciprofloxacin, for recurrent UTIs. She had previously been prescribed an oral contraceptive for dysmenorrhea, but it was recently discontinued due to severe nausea and negligible improvement of her abdominal pain", "she had no family history of porphyria, history of skin lesions, previous hospitalizations due to abdominal pain, history of urinary color changes, or any prior positive urine cultures within our medical institution" ]

[ "alert and oriented to time, place, and person without any objective signs of anxiety, depression, psychosis, or other appreciable psychiatric disturbances" ]

[ "Laboratory examinations were remarkable only for hyponatremia of 130 mEq / L and hypoalbuminemia at 3.4 g / dL. Urine analysis with reflex culture was negative for leukocyte esterase and nitrites. Urine osmolality was 410 mOsm / kg and urine sodium was 100 mEq / L", "Her initial computerized tomography ( CT ) scan of the abdomen and pelvis ( Figure 1 ) revealed a diffusely dilated small bowel filled with fecal matter and marked colonic distention with cecal dilatation measuring 9 cm", "Rapid stool studies were obtained and returned positive for Clostridium difficile antigen and toxin A&B.", "A repeat CT scan of her abdomen ( Figure 2 ) noted no further small bowel dilation, free air, or free fluid. CT enterography showed no bowel wall thickening or imaging features to suggest inflammatory bowel disease", "A random urine PBG was elevated at 99.9 mg / g ( normal < 0.22 mg / g ), with a urine delta aminolevulinic acid ( ALA ) elevated at 71.9 mg / g ( normal < 5.4 mg / g ). The fractionation of porphyrins in plasma ( Table 1 ) and urine ( Table 2 ) was suggestive of a biochemical diagnosis of AIP" ]

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[ "dysmenorrhea and recurrent urinary tract infections ( UTIs ),", "recurrent UTIs", "dysmenorrhea", "hyponatremia of 130 mEq / L", "Urine analysis with reflex culture was negative for leukocyte esterase and nitrites. Urine osmolality was 410 mOsm / kg and urine sodium was 100 mEq / L", "no family history of porphyria, history of skin lesions, previous hospitalizations due to abdominal pain, history of urinary color changes, or any prior positive urine cultures" ]

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[ "22 - year - old" ]

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[ "biochemical diagnosis of AIP ." ]

[ "Intravenous ( IV ) hematin 1 mg / kg / d and IV dextrose were given for 3 days . After hematin / dextrose therapy , her abdominal pain and bowel symptoms resolved" ]

[ "low hemoglobin ( 9.5 g / dL )" ]

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[ "A 12‐year‐old girl, born from consanguineous marriage, was presented with a five‐year progressing bilateral, symmetrical, hyperpigmented, and thickened patches with hypertrichosis. These lesions were present not only in the inner thighs but also in pubic and lumbar regions." ]

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[ "A four‐mm punch biopsy showed perifollicular focal para‐keratotic hyperkeratosis of the epidermis. The dermis was slightly edematous and contain ectatic capillaries. There was a lymphocytic and histiocytic infiltrate ( Figure 4 ). IHC was positive for CD68", "Biological data showed low hemoglobin ( 9.5 g / dL ) and high erythrocyte sedimentation rate ( 75 mm / h ). The rest of laboratory tests including thyroid function tests, lipid profile, liver function tests, renal function tests, and antinuclear antibodies profile were all normal. Echocardiography and electrocardiogram were normal. Abdominal ultrasound found small uterus and ovaries with thickened skin and subcutis of vulva. Genetic analysis revealed homozygous missense mutation c.1088G > A; p. Arg363GIn in exon 6 in linkage disequilibrium with the same non‐pathogenic variant at intron 2 c.300 + 3A > G." ]

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[ "hyperpigmentation of labia majora" ]

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[ "finger and toe flexion contracture ( camptodactyly and hallux valgus )" ]

[ "deformation of teeth", "hearing loss in the early childhood", "Ophthalmological examination showed chorioretinal atrophy" ]

[ "five‐year progressing bilateral, symmetrical, hyperpigmented, and thickened patches with hypertrichosis. These lesions were present not only in the inner thighs but also in pubic and lumbar regions", "gluteal lipodystrophy, swelling with hyperpigmentation of labia majora", "Erythematous, annular, and figurate lesions slightly keratotic without atrophy were present in cheeks and nose ( Figure 2 ). Dermoscopy revealed multiple telangiectasias drawing a reticulated network ( Figure 3 ). A four‐mm punch biopsy showed perifollicular focal para‐keratotic hyperkeratosis of the epidermis. The dermis was slightly edematous and contain ectatic capillaries. There was a lymphocytic and histiocytic infiltrate ( Figure 4 ). IHC was positive for CD68", "presence of erythematous annular and figurate lesions that were slightly keratotic in cheeks and nose" ]

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[ "12‐year‐old" ]

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[ "H Syndrome was diagnosed based on histological , immunohistochemical ( IHC ) examination and molecular analysis ." ]

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[ "A 31‐year‐old mentally disabled man was referred to our neurologic clinic with a gradually worsening gait disorder, impaired balance, and repeated falling episodes. The patient was the third child of consanguinity marriage. He was delivered following a normal term pregnancy with normal birthweight and height. History of atheromatous disease or intractable infantile‐onset diarrhea was not distinguished. At the age of five, he developed a blurred vision, which was diagnosed as a bilateral cataract. The patient was a school dropout due to intellectual and neuropsychiatric disability. He had developmental delays in the mental functioning and speech with a normal physical growth. At the age of 20, he developed bilateral tendinous swelling of the posterior part of the ankles that worsened over time. He complained of severe gait disturbance and ataxia since 3–4 years ago. He had frequent falling episodes resulting in multiple bone fractures. Gait disorder worsened gradually, and he started using a wheelchair.", "The patient was married, but he was infertile" ]

[ "gradually worsening gait disorder, impaired balance, and repeated falling episodes", "school dropout due to intellectual and neuropsychiatric disability. He had developmental delays in the mental functioning and speech", "severe gait disturbance and ataxia since 3–4 years ago. He had frequent falling episodes", "Gait disorder worsened gradually, and he started using a wheelchair.", "muscle weakness predominant in the distal muscles of upper and lower limbs ( MRC score of 3 in the foot dorsiflexion and MRC score 2 in the finger adduction and abduction ), hypertonia, brisk deep tendon reflexes, bilateral Babinski sign, and ankle clonus. The finger to nose was normal, but the heel to shin was abnormal bilaterally", "A brain magnetic resonance imaging ( MRI ) discovered cerebral and cerebellar atrophy, high‐intensity areas in the dentate nuclei, and symmetric hyperintensities in the cerebellar deep white matter and paraventricular white matter on T2‐weighted ( T2W ) and fluid‐attenuated inversion recovery ( FLAIR ) images with corresponding hypointensities on T1‐weighted ( T1W ) images" ]

[ "The laboratory results were normal for the thyroid, liver, and kidney function, serum electrolytes, and triglyceride and cholesterol level. A brain magnetic resonance imaging ( MRI ) discovered cerebral and cerebellar atrophy, high‐intensity areas in the dentate nuclei, and symmetric hyperintensities in the cerebellar deep white matter and paraventricular white matter on T2‐weighted ( T2W ) and fluid‐attenuated inversion recovery ( FLAIR ) images with corresponding hypointensities on T1‐weighted ( T1W ) images ( Figure 2 ). Ultrasonography demonstrated focal areas of hypoechogenicity on the bilateral Achilles tendons measuring 3, 7, 9, 12, and 16 mm on the right and 8, 15, 11, and 14 mm on the left side. Whole‐exome sequencing identified a homozygous splicing mutation, NM_000784 : exon3 : c.465C > A; ( p. Tyr155 * ) in CYP27A1 gene compatible with a diagnosis of CTX.", "Sex hormone tests were normal. Testicular ultrasound showed that the size of the testes was in the lower limit of normal range with a normal epididymis and vein plexus. Semen analysis showed azoospermia. Analysis of the most common Y chromosome microdeletions using multiplex polymerase chain reaction and gel electrophoresis showed no microdeletions in AZFa, AZFb, and AZFc sub‐regions of the long arm of chromosome Y." ]

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[ "he was infertile", "Testicular ultrasound showed that the size of the testes was in the lower limit of normal range with a normal epididymis and vein plexus. Semen analysis showed azoospermia." ]

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[ "bilateral tendinous swelling of the posterior part of the ankles that worsened over time", "multiple bone fractures", "bilateral and symmetrical painless hypertrophy of the Achilles tendons", "muscle weakness predominant in the distal muscles of upper and lower limbs ( MRC score of 3 in the foot dorsiflexion and MRC score 2 in the finger adduction and abduction ),", "focal areas of hypoechogenicity on the bilateral Achilles tendons measuring 3, 7, 9, 12, and 16 mm on the right and 8, 15, 11, and 14 mm on the left side" ]

[ "blurred vision, which was diagnosed as a bilateral cataract." ]

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[ "He was delivered following a normal term pregnancy with normal birthweight and height." ]

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[ "31‐year‐old" ]

[ "of five" ]

[ "diagnosis of CTX ." ]

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[ "his weight was 54 kg ( 11.70 percentile ), height was 158 cm ( 1.07 percentile ), and head circumference was 56 cm" ]

[ "diarrhea and jaundice" ]

[ "A 17 - year - old intellectually disabled boy was admitted to our neurology clinic due to an abnormality in his hand and difficulty in walking. He had a feeling of fear and trembling of his legs when climbing the stairs. His symptoms had begun when he was 4 years old and worsened until his parents noted and brought him to the clinic. He had diarrhea and jaundice during infancy and underwent phototherapy 3 times until the jaundice was completely resolved. Also, he had bilateral cataracts at the age of 12. At the age of 14, he had a car accident that caused a fracture in his skull. He had no history of cardiovascular or pulmonary diseases, and there was no genetic disorder in his family history. He was the fourth child of the third - degree consanguineous marriage and was born at term after a normal pregnancy, and his development was normal." ]

[ "intellectually disabled", "abnormality in his hand and difficulty in walking. He had a feeling of fear and trembling of his legs when climbing the stairs", "development was normal", "ataxia, dysarthria, and spastic paraparesis with pyramidal signs more prominent on the right lower extremity", "peripheral neuropathy, hallucinations, depression, and delusion", "Electromyography and nerve conduction velocity ( EMG / NCV ) revealed no evidence of myopathy or neuropathy, and the motor and sensory conduction velocities were normal", "Brain magnetic resonance imaging ( MRI ) demonstrated diffuse and focal cerebral and cerebellar white matter abnormalities", "absence of seizures", "intellectual disability" ]

[ "Laboratory tests showed a normal cholesterol level in the serum ( 162 mg / dL ) and a normal total serum bile acid level ( 10 µmol / L )", "Brain magnetic resonance imaging ( MRI ) demonstrated diffuse and focal cerebral and cerebellar white matter abnormalities", "The genetic study was performed by the next - generation sequencing ( NGS ) method, and the results were confirmed by the Sanger sequencing method. The apparent homozygous variants in the NM_000784.4(CYP27A1 ) : c.803G > A ( p. Trp268 * ) and NM_032382.5(COG8 ) : c.1073G > A ( p. Arg358Gln ) in the CYP27A1 and COG8 genes were found which are pathogenic based on American College of Medical Genetics ( ACMG ) classification.", "In a 3 - month follow - up, he had a cholesterol level of 96 mg / dL and a bile acid level of 4 µmol / L which both were normal" ]

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[ "car accident that caused a fracture in his skull", "no sign of palpable xanthoma in any of his tendons even in Achilles tendon. In the examination of his right hand, the fourth and fifth interphalangeal joints were flexed, and the third and fifth metacarpophalangeal joints were extended, which was found to be the result of presence of small xanthoma in the tendons of the right hand" ]

[ "bilateral cataracts", "visual impairment" ]

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[ "born at term after a normal pregnancy" ]

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[ "17 - year - old" ]

[ "infancy" ]

[ "our patient was diagnosed with CTX and a mutation on COG8 gene" ]

[ "In due course , we started CDCA 810 mg daily ( 15 mg / kg / day ) ." ]

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[ "A 33 - year - old woman was admitted to the psychiatric acute ward with the following symptoms : delusions of persecution, auditory hallucination, impulsive behavior, and emotional instability. There was no family history of psychiatric diseases", "At age 18, she underwent cataract surgery, and at age 26, she underwent cholecystectomy for cholestasis" ]

[ "was admitted to the psychiatric acute ward with the following symptoms : delusions of persecution, auditory hallucination, impulsive behavior, and emotional instability. ',", "admitted to the psychiatric ward for presentation of delusions, hallucinations, and behavioral disturbance is reported.", "cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood.", "the patient was diagnosed with organic schizophrenia - like disorder", "During hospitalization in the psychiatric ward, the patient ’s brief psychiatric rating sale ( BPRS ) score was 40, her Wechsler intelligence scale score was 65", "Nervous system examination showed normal muscle tone in the extremities, grade 5 muscle strength, instability in the heel - knee - tibia test of the right lower extremity, and a positive Romberg sign. In the mental status examination, the patient exhibited the following : verbal auditory hallucination; delusions of persecution; negative perceptions; irritability; childish emotions; poor general knowledge, understanding, judgment, and calculation; impulsivity; and lack of insight", "For 6 mo, the patient showed hostility towards her colleagues, firmly believing that they wanted to harm her. She could hear abusive voices of colleagues when she was alone. The false belief and voice interfered with the social relations and behavior of the patient, leading to outrunning behavior. In addition, the patient exhibited impulsive acts and temperamental behavior, such as tearing people 's clothes, smashing things, standing outside naked when she became excited, and running around at midnight. She also experienced severe depression for several days, with crying and expressing a desire to commit suicide by euthanasia. \"", "According to her mother, the patient has been weak and obtuse since childhood and was unable to pass primary school exams. She required supervision and care from her family in her personal life. Despite being able to work, she could not perform her job well and did not get along with her colleagues, leading to her dismissal from several companies.", "skewed walking to the right side 5 years ago" ]

[ "total biliary acid returned to normal levels", "Brain magnetic resonance imaging ( MRI ) revealed symmetrical patchy abnormal signals in the dentate nuclei and deep medulla of the bilateral cerebellar hemispheres. These signals exhibited a slight decrease in signal intensity on T1 - weighted images ( T1WI ) ( Figure 2A ) and a slight increase in signal intensity on fluid attenuated inversion recovery ( FLAIR ) ( Figure 2B ). Left - ankle - joint MRI showed that the inhomogeneous area had a considerable local thickening of the left Achilles tendon. The area displayed clear boundaries measuring approximately 6.6 cm × 1.2 cm and exhibited a slightly elevated signal intensity on T1WI and a similar slightly elevated signal intensity on the proton density weighted image, accompanied by linear hypointensity within ( Figure 1B ). Brain magnetic resonance spectroscopy ( MRS ) showed decreases in N - acetylaspartate ( NAA ) intensities and increases in lactate and lipid signals", "the total biliary acid level returned to normal", "biochemical tests revealed an elevated total biliary acid level of 11.2 µmol / L ( normal value ≤ 10.0 ) and decreased levels of chenodeoxycholic acid and ursodeoxycholic acid. Subsequently, a biopsy of the left Achilles tendon was performed, revealing numerous lipid crystals and a few foamy macrophages ( Figure 1A ). The patient underwent genetic analysis, which identified two mutations in the CYP27A1 gene associated with CTX : c.1263 + 3G > C and c.379C > T." ]

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[ "Achilles tendon xanthoma", "normal muscle tone in the extremities, grade 5 muscle strength", "Left - ankle - joint MRI showed that the inhomogeneous area had a considerable local thickening of the left Achilles tendon. The area displayed clear boundaries measuring approximately 6.6 cm × 1.2 cm and exhibited a slightly elevated signal intensity on T1WI and a similar slightly elevated signal intensity on the proton density weighted image, accompanied by linear hypointensity within", "patient has been weak", "swelling in her left Achilles tendon, pain, and skewed walking to the right side", "biopsy of the left Achilles tendon was performed, revealing numerous lipid crystals and a few foamy macrophages" ]

[ "cataract", "cataract" ]

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[ "33 - year - old", "33 - year - old" ]

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[ "the patient ’s history of CTX was identified", "On the basis of these findings , the patient was ultimately diagnosed with CTX" ]

[ "prescribed chenodeoxycholic acid ( 750 mg / d )" ]

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[ "6 year history of increased laxity of the skin over the neck, thighs, and abdomen. The patient gave a history of blurring of vision, photophobia, and headache for the past 1 week" ]

[ "headache", "no history of breathlessness, chest pain, palpitations, claudicating pain, or neurological deficits" ]

[ "2D - echo and electrocardiogram were investigated to check for cardiac involvement but were normal", "A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid - dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material ( mucin ). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition" ]

[ "no history of breathlessness, chest pain, palpitations, claudicating pain", "2D - echo and electrocardiogram were investigated to check for cardiac involvement but were normal." ]

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[ "no history of breathlessness, chest pain" ]

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[ "blurring of vision, photophobia", "Fundus examination of both eyes showed dark brownish - red, irregular streaks surrounding and extending radially from the optic disc, suggestive of angioid streaks" ]

[ "6 year history of increased laxity of the skin over the neck, thighs, and abdomen", "prominent skin folds, skin laxity, and wrinkles were noted over the right side of the neck, abdominal folds, thighs, and groin. A single, skin - colored papule of a size of 2 mm was present over the right lower lid, near the medial canthus, and similar skin - colored to yellowish papules of a size of 1.5–2 mm were noted over the neck and face", "A skin biopsy was performed from the neck, which showed an unremarkable epidermis. Degenerate basophilic collagen bundles were noted in the mid - dermis and lower dermis with intervening sclerotic areas that were seen extending to the lower dermis. Certain areas in the dermis showed a pale interstitial material ( mucin ). Verhoeff Van Gieson staining showed elastic fibers with a short and curled appearance. Von Kossa staining was performed, and it showed evidence of calcium deposition" ]

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[ "38 - year - old" ]

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[ "Based on the clinical and histopathological findings , a diagnosis of PXE was made ." ]

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[ "blood pressure was elevated measuring 150/100 mm Hg on the left and 144/100 mm Hg on the right arm, the rest of the vitals were stable. His body weight was 42.5 kg ( 75th-90th centile ) and his height measured 138 cm ( 50th centile )" ]

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[ "history of bilateral scrotal enlargement noticed in the past 3 months. History of palpitation, restlessness, anger, and dizziness on and off for the past 4 - 5 years" ]

[ "restlessness, anger, and dizziness" ]

[ "The patient presented to our department for ultrasonography of the inguinoscrotal region. Bilateral testis was normal in size ( right and left testicular volume – 2.9 mL and 2.8 mL respectively ) with multiple well - defined round to oval hetero - echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity ( Figs. 1 A, B and 2 A, B ). On screening abdominal sonography, a large well - defined triangular hypoechoic lesion was noted in the left suprarenal region and a smaller similar lesion in the right suprarenal region without internal vascularity", "Contrast - enhanced CT abdomen and pelvis were performed which showed homogeneously enhancing enlarged bilateral adrenal glands ( left > right ) with maintained shape, suggesting adrenal hyperplasia ( Fig. 4 A ). Bilateral testes appeared hypodense with multiple enhancing nodules within ( Fig. 4 B and C ). Serum tumor markers ( alpha - fetoprotein, LDH, and Beta hCG ) were negative", "Grayscale US of scrotum showing normal - sized right testis with heterogeneous appearance. ( B ) US image of bilateral testes with multiple nodules containing tiny calcific foci ( black arrow ). Fig 1 Fig. 2 ( A ) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. ( B ) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity. Fig 2 Fig. 3 ( A ) Grayscale US of the abdomen showing triangular hypoechoic lesions in right suprarenal regions ( white arrow ). ( B ) Grayscale US of the abdomen showing triangular hypoechoic lesions in left suprarenal regions ( white arrow ). Fig 3 Fig. 4 ( A ) Contrast enhanced computed tomography ( CECT ) image of abdomen in coronal reformatted section showing bilateral adrenal hyperplasia ( White arrows ). ( B ) CECT pelvis axial section showing multiple enhancing nodules in the right testis ( black arrow ). ( C ) CECT pelvis axial section showing multiple enhancing nodules in left testis ( black arrow ). Fig 4 X - ray left wrist AP / lateral view was done for estimating the bone age which showed accelerated bone age corresponding to approximately 18 years of age ( Fig. 5 ). The serum potassium concentration was found to be elevated at 5.8 mEq / L ( normal range : 3.5 - 4.5 mEq / L ), whereas the sodium level remained within normal limits at 140 mEq / L. There was a significantly heightened level of 17 - hydroxyprogesterone at 1800 ng / dL ( normal range : < 110 ng / dL ), accompanied by normal levels of lactate dehydrogenase ( LDH ), beta - human chorionic gonadotropin hormone ( B - HCG ), and alpha - fetoprotein ( AFP ). Additionally, the serum adrenocorticotropic hormone ( ACTH ) concentration was elevated, measuring 564 pg / mL ( normal range : 7.2 - 63.3 pg / mL ), while cortisol levels were diminished, measuring 5.7 µg / dL ( normal range : 7 - 25 µg / dL ). Dehydroepiandrosterone sulfate ( DHEA - S ) was measured at 5.25 µmol / L ( normal range : ≤ 3.726 µmol / L ), reflecting an increase. Moreover, androstenedione levels were elevated at 250 ng / dL ( normal range : 31 - 65 ng / dL ), and there was a reduced level of Inhibin B, measuring 71.1 pg / mL ( normal range : 240 - 445 pg / mL )." ]

[ "palpitation" ]

[ "Tanner staging was done which was stage 3 for genitalia ( testis length 3.5 cm, penile length 10 cm ) and stage 3 for pubic hair." ]

[ "bilateral scrotal enlargement", "bilateral scrotal swelling with normal - appearing skin, and bilateral testes were firm on palpation. No localized rise in temperature or tenderness was noted. Tanner staging was done which was stage 3 for genitalia ( testis length 3.5 cm, penile length 10 cm ) and stage 3 for pubic hair", "Bilateral testis was normal in size ( right and left testicular volume – 2.9 mL and 2.8 mL respectively ) with multiple well - defined round to oval hetero - echoic nodules with calcific foci within and color Doppler showed increased peripheral and internal vascularity", "Bilateral testes appeared hypodense with multiple enhancing nodules within", "Grayscale US of scrotum showing normal - sized right testis with heterogeneous appearance. ( B ) US image of bilateral testes with multiple nodules containing tiny calcific foci ( black arrow ). Fig 1 Fig. 2 ( A ) Color Doppler US of scrotum showing iso to heteroechoic nodules within right testis with increased vascularity. ( B ) Color Doppler US of scrotum showing iso to heteroechoic nodules within left testis with increased vascularity", "CECT pelvis axial section showing multiple enhancing nodules in the right testis ( black arrow ). ( C ) CECT pelvis axial section showing multiple enhancing nodules in left testis", "serum potassium concentration was found to be elevated at 5.8 mEq / L ( normal range : 3.5 - 4.5 mEq / L ), whereas the sodium level remained within normal limits at 140 mEq / L." ]

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[ "Generalized skin hyperpigmentation was present" ]

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[ "11 - year - old" ]

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[ "these findings point towards a diagnosis of congenital adrenal hyperplasia" ]

[ "The patient is currently undergoing treatment with hydrocortisone and is on regular follow - up . The 3 - month follow - up revealed clinical improvement with a reduction in testis size and decreased ACTH levels , indicating positive progress ." ]

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[ "recurring episodes of intense abdominal pain", "uncontrollable vomiting" ]

[ "We present the case of a 28‐year‐old Mexican woman who came to our clinic because she had been experiencing recurring episodes of intense abdominal pain, weakness in her upper and lower extremities, uncontrollable vomiting, and insomnia since the age of 17. These symptoms required frequent visits to the emergency department", "abdominal surgery for suspected acute appendicitis", "However, subsequent years witnessed progressively severe crises, some accompanied by paralysis and kidney injury", "Notably, her first cousin was also diagnosed with AIP and had a similar clinical presentation", "Over the past years, her symptoms have been sporadic, and she has not required hospitalization" ]

[ "weakness in her upper and lower extremities", "insomnia", "paralysis" ]

[ "episode of elevated urine PBG during a crisis", "elevated urine PBG was even detected during asymptomatic periods.", "This analysis revealed a heterozygous state mutation, c.457C > T ( p. Q153, exon 9, HMBS gene" ]

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[ "weakness in her upper and lower extremities" ]

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[ "28‐year‐old" ]

[ "age of 17" ]

[ "confirmed the diagnosis of AIP" ]

[ "Treatment with hematin derivatives ( Normosang ® , Panhematin ® ) was initiated , resulting in partial improvement", "At the age of 38 , she enrolled in a clinical trial for Givosiran , an RNA interference therapeutic targeting ALAS1 mRNA . Remarkably , she exhibited a notable response to the treatment and continued it even after the trial" ]

[ "systolic blood pressure 180 mm Hg" ]

[ "worsening abdominal pain", "abdominal pain was severe, generalized, non - radiating and associated with constipation" ]

[ "A 26 - year - old female with past medical history of ruptured ovarian cyst, currently on oral contraceptive medications ( OCPS ), presented with a 5 - day history of worsening abdominal pain. Prior to presenting to our hospital, she had sought medical attention on multiple occasions at several other facilities.", "The abdominal pain was severe, generalized, non - radiating and associated with constipation. Of note, the patient had recently been engaging in significant exercises, and was in the luteal phase of her menstrual cycle" ]

[ "tingling sensation in her hands", "seizure and postictal confusion", "Magnetic Resonance ( MR ) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES" ]

[ "Multiple pelvic examinations and 3 computerized tomography ( CT ) imaging studies were unremarkable. A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen", "initial laboratory studies showed hypokalemia ( potassium 3.4 mmol / L, reference range 3.5–5.1 mmol / L ), and an elevated creatinine 1.14 mg / dl ( baseline around 0.80 mg / dl ). Pelvic examination was again benign. A small bowel followthrough showed significant delay in contrast transit", "serum sodium decreased abruptly from 136 mmol / L to 127 mmol / L ( range : 135–145 mmol / L ). Serum osmolality was low at 271 mOsm / kg ( range : 280–300mOsm / kg ), urine sodium was markedly elevated at 168 mmol / L and urinalysis was remarkable for increased urine specific gravity ( > 1.042 )", "Magnetic Resonance ( MR ) imaging showed subtle symmetric parenchymal edema in the occipital and posterior parietal lobes, suggestive of PRES", "urine porphobilinogen was measured and was found to be elevated at 188.4 mg / L ( range : 0.0–2.0 mg / L ). 24 - hour urine Uroporphyrin was also significantly elevated at 135.6mg/24hr ( range : 0.0–1.5mg/24hr )" ]

[ "significant hypertension ( systolic blood pressure 180 mm Hg )" ]

[ "serum sodium decreased abruptly from 136 mmol / L to 127 mmol / L ( range : 135–145 mmol / L ). Serum osmolality was low at 271 mOsm / kg ( range : 280–300mOsm / kg ), urine sodium was markedly elevated at 168 mmol / L and urinalysis was remarkable for increased urine specific gravity ( > 1.042 ).", "Syndrome of Inappropriate Antidiuretic Hormone secretion ( SIADH )" ]

[ "ruptured ovarian cyst,", "A bedside transvaginal ultrasound showed an ovarian cyst, but no other concerning findings were seen", "was in the luteal phase of her menstrual cycle", "hypokalemia ( potassium 3.4 mmol / L, reference range 3.5–5.1 mmol / L ), and an elevated creatinine 1.14 mg / dl ( baseline around 0.80 mg / dl ).", "red discoloration of urine" ]

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[ "acute visual disturbances" ]

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[ "26 - year - old" ]

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[ "acute porphyria" ]

[ "Hemin treatment was unavailable at our facility" ]