3β‐hydroxy‐Δ<sup>5</sup>‐C<sub>27</sub>‐steroid dehydrogenase/isomerase deficiency in a patient who underwent oral bile acid therapy for 10 years and delivered two healthy infants

Nittono, Hiroshi; Takei, Hiroyuki; Unno, Atsushi; Shimizu, Toshiaki; Kobayashi, Masakazu; Koike, Masato; Murai, Tsuyoshi; Kurosawa, Takao; Thoma, Masahiko

doi:10.1111/j.1442-200x.2010.03131.x

Cited by 7 publications

(7 citation statements)

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“…As seen in our previous case reports, in the present study higher proportions of the unusual BA were detected than of the usual BA. For example, there were high levels of Δ 5 ‐diol‐ and Δ 5 ‐triol‐BA in the 3β‐HSD samples, of Δ 5 ‐ol BA in the oxysterol 7α‐deficiency samples, and of Δ 4 ‐BA in the 5β‐reductase deficiency samples . Patient 1 was lost to follow up; similarly, the prognosis of patient 2 is unknown, because no further medical records were obtained from his doctor.…”

Section: Discussionsupporting

confidence: 90%

Use of dried urine spots for screening of inborn errors of bile acid synthesis

Naritaka

Suzuki

Takei

et al. 2019

Pediatrics International

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Background In pediatric patients with cholestasis of unknown cause, inborn errors of bile acid (BA) synthesis (IEBAS) may be considered. For the initial screening for IEBAS, clarification of the urine BA profile is essential. The transportation of urine in a frozen state via air delivery, however, is laborious and costly. This study assessed the feasibility of using dried urine spots (DUS) to establish a more convenient and affordable method of IEBAS screening. Methods We created DUS using urine samples from patients with 3β‐hydroxy‐Δ5‐C27‐steroid dehydrogenase/isomerase deficiency (3β‐HSD) and Δ4‐3‐oxo‐steroid 5β‐reductase deficiency as standard preparations. We started accepting DUS specimens by regular mail. Results The ratio of unusual to usual BA is essential for the initial detection of IEBAS, and the recovery rates of abnormal BA were acceptable. The recovery rate of Δ4‐BA on day 28 decreased to 31.8% at 25°C, and to 19.6% at 37°C. Therefore, the sending of DUS should be avoided under conditions of high temperature. Of a total of 49 children with cholestasis, eight new patients were diagnosed with IEBAS using this screening method. Conclusion The mailing screening system is expected to facilitate the shipment, from regions outside of Japan, of samples for IEBAS screening.

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Section: Discussionsupporting

confidence: 90%

Use of dried urine spots for screening of inborn errors of bile acid synthesis

Naritaka

Suzuki

Takei

et al. 2019

Pediatrics International

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“…Patients with 3β‐HSD deficiency can differ widely in presenation. Some patients present with signs of liver disease (jaundice, hepatosplenomegaly), others with fat soluble vitamin deficiencies (hypocalcemia, rickets, coagulopathy) or fat malabsorption as a result of cholestasis, or a combination of these features 2, 3, 6‐16, 18. The proband in our family did not have clinical evidence of cholestasis at presentation, although her bilirubin level was mildly elevated.…”

Section: Discussionmentioning

confidence: 99%

“…The diagnosis was established by measuring bile acids in the urine using mass spectrometry in a consanguineous Saudi Arabian family in which several family members presented as neonates with giant cell hepatitis and bridging cirrhosis 5. Over 50 patients with this disorder from at least 40 unrelated families have subsequently been reported 3, 6‐1617 and 21 different mutations have been described that cause 3β‐HSD deficiency 3, 6, 7, 12, 13…”

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confidence: 99%

Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology

et al. 2012

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The most common inborn error of bile acid metabolism is 3β-hydroxy-Δ5-C27-steroid oxidoreductase (3β-HSD) deficiency, a disorder that usually presents in early childhood with hepatic dysfunction. Timely diagnosis of this disorder is crucial since it can be effectively treated with primary bile acid replacement. Here we describe a 24-year-old woman from Iran with cirrhosis of unknown etiology. Her sister and a first cousin died of cirrhosis (ages 19 and 6 years) and another 32-year old first cousin had a self-limited liver disorder in childhood that resolved at age 9 years. The family history was consistent with the notion that affected family members were homozygous for a mutant allele inherited identical-by-descent. A genome-wide analysis of 2.5 million single nucleotide polymorphisms (SNP) was performed to identify regions of homozygosity that were present in the proband and the 32-year old first cousin, but not in a healthy relative. One of these regions contained the gene encoding 3β-HSD (HSD3B7). Sequence analysis of HSD3B7 revealed that the proband and her 32-year old cousin were homozygous for a frame shift mutation (c.45_46del AG, p.T15Tfsx27) in exon 1. The diagnosis of 3β-HSD deficiency was confirmed by documenting high levels of 3β-hydroxy-Δ5 bile acids in the serum of the first cousin using mass spectrometry. To our knowledge, the 32-year old relative in this family represents the oldest asymptomatic patient with this disorder. Conclusion: This study highlights the clinical utility of homozygosity mapping in diagnosing autosomal recessive metabolic disorders. This family illustrates the wide variation in expressivity that occurs in 3β-HSD deficiency and underscores the need to consider a bile acid synthetic defect as a possible cause of liver disease in adults.

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“…In group LT/died, despite all patients (apart 2 cases, cases 19 and 54) were diagnosed and given oral BA replacement treatment when they were fewer than 1 year, the prognoses were poor. However, some cases (case 20) and other reported cases could be alive until adolescence and adult without any BA replacement treatment [16,25,26] . We speculated that the variable phenotypes conceivably were the consequence of heterogeneous molecular basis.…”

Section: Discussionmentioning

confidence: 91%

Prognosis and clinical characteristics of patients with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency diagnosed in childhood

Zhang¹,

Yang²,

Wang³

et al. 2022

Medicine

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Objectives:3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency is a rare autosomal recessive condition. So far fewer than 100 cases have been reported and the factors affecting the prognosis are not yet established. The objective of this study is to explore a possible prediction of the outcome of this rare condition.Methods:This review was undertaken and reported in accordance with the preferred reporting items for systematic review and meta-analyses guidelines. Demographics, clinical features, gene data, treatment strategies and prognoses at the last follow-up were extracted and summarized. Patients were divided into 2 groups (alive with native liver and liver transplantation/died). Risk factors for the different clinical features were identified.Results:87 patients that were taken from 7 case reports and 9 case series were included. 38 (38/63, 63.0%) of them presented initial symptoms when they were younger than 1 month and 55 (55/63, 87.3%) less than 1 year. There is a larger proportion of patients younger than 1 month or 1 year at the age of symptom onset in the liver transplantation /died group than patients in alive with the native liver group. The majority of patients (53/62, 85.5%) were diagnosed before the age of 5 year. In all cases, 65 (predicted) pathogenic variants have been identified. Over 70% of patients carried an HSD3B7 variant on exon 1, 4, 5 or 6. 71 (81.6%) were alive at the last follow-up, 16 (18.4%) underwent liver transplantation or died. No significance was found between the group alive with native liver and group liver transplantation /died.Conclusion:Age of onset of the symptoms may be a potential factor that determines the outcome of patients with 3β-HSD deficiency, patients presented with symptoms and signs at an age younger than 1 month or even 1 year may have a worse prognosis. Since there is no difference between clinical outcome and zygosity of gene mutation, we recommend a further study about any possible relationship between mutation site and clinical characteristics or prognosis.

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3β‐hydroxy‐Δ⁵‐C₂₇‐steroid dehydrogenase/isomerase deficiency in a patient who underwent oral bile acid therapy for 10 years and delivered two healthy infants

Cited by 7 publications

References 9 publications

Use of dried urine spots for screening of inborn errors of bile acid synthesis

Use of dried urine spots for screening of inborn errors of bile acid synthesis

Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology

Prognosis and clinical characteristics of patients with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency diagnosed in childhood

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3β‐hydroxy‐Δ5‐C27‐steroid dehydrogenase/isomerase deficiency in a patient who underwent oral bile acid therapy for 10 years and delivered two healthy infants

Cited by 7 publications

References 9 publications

Use of dried urine spots for screening of inborn errors of bile acid synthesis

Use of dried urine spots for screening of inborn errors of bile acid synthesis

Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology

Prognosis and clinical characteristics of patients with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency diagnosed in childhood

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3β‐hydroxy‐Δ⁵‐C₂₇‐steroid dehydrogenase/isomerase deficiency in a patient who underwent oral bile acid therapy for 10 years and delivered two healthy infants