Zhao J, Fang LJ, Setchell KD, Chen R, Li LT, Wang JS. Primary ∆4-3-oxosteroid 5β-reductase deficiency: Two cases in China. World J Gastroenterol 2012; 18(47): 7113-7117 [PMID: 23323017 DOI: 10.3748/wjg.v18.i47.7113]
Corresponding Author of This Article
Jian-She Wang, Professor, Center for Pediatric Liver Disease, Children’s Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai 201102, China. jshwang@shmu.edu.cn
Article-Type of This Article
Case Report
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World J Gastroenterol. Dec 21, 2012; 18(47): 7113-7117 Published online Dec 21, 2012. doi: 10.3748/wjg.v18.i47.7113
Primary ∆4-3-oxosteroid 5β-reductase deficiency: Two cases in China
Jing Zhao, Ling-Juan Fang, Kenneth DR Setchell, Rui Chen, Li-Ting Li, Jian-She Wang
Jing Zhao, Ling-Juan Fang, Rui Chen, Li-Ting Li, Jian-She Wang, Center for Pediatric Liver Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
Kenneth DR Setchell, Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
Jian-She Wang, Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai 201508, China
Author contributions: Wang JS contributed to study design, patients’ management and supervised the genetic studies; Zhao J contributed to literature research, genetic studies, data analysis and manuscript preparation; Fang LJ contributed to samples collection and genetic studies; Setchell KDR contributed to the analysis and interpretation of urinary bile acids; Chen R and Li LT contributed to patients follow-up.
Supported by National Natural Science Foundation of China, No. 81070281
Correspondence to: Jian-She Wang, Professor, Center for Pediatric Liver Disease, Children’s Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai 201102, China. jshwang@shmu.edu.cn
Telephone: +86-21-64931171 Fax: +86-21-64931901
Received: July 25, 2012 Revised: November 12, 2012 Accepted: November 24, 2012 Published online: December 21, 2012
Abstract
Aldo-keto reductase 1D1 (AKR1D1) deficiency, a rare but life-threatening form of bile acid deficiency, has not been previously described in China. Here, we describe the first two primary ∆4-3-oxosteroid 5β-reductase deficiency patients in Mainland China diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis. A high proportion of atypical 3-oxo-∆4-bile acids in the urine indicated a deficiency in ∆4-3-oxosteroid 5β-reductase. All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient’s parents. One patient exhibited compound heterozygous mutations: c.396C>A and c.722A>T, while the other was heterozygous for the mutation c.797G>A. Based on these mutations, a diagnosis of primary ∆4-3-oxosteroid 5β-reductase deficiency could be confirmed. With ursodeoxycholic acid treatment and fat-soluble vitamin supplements, liver function tests normalized rapidly, and the degree of hepatomegaly was markedly reduced in both patients.
