Primary 4-3-oxosteroid 5β-reductase deficiency：Two cases in China
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...
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| Published in | World journal of gastroenterology : WJG Vol. 18; no. 47; pp. 7113 - 7117 |
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| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
United States
Baishideng Publishing Group Co., Limited
21.12.2012
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| Subjects | |
| Online Access | Get full text |
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| Summary: | 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.396CA and c.722AT,while the other was heterozygous for the mutation c.797GA.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. |
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| Bibliography: | 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.396CA and c.722AT,while the other was heterozygous for the mutation c.797GA.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. Jing Zhao, Ling-Juan Fang, Kenneth DR Setchell, Rui Chen, Li-Ting Li, Jian-She Wang（Center for Pediatric Liver Diseases, Children＇s Hospitalof Fud＇an University, Shanghai 201102, China; Department of Pathology and Laboratory Medicine, Cincinnati Children＇s Hospital Medical Center, Cincin- nati, OH 45229, United States; Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai 201508, China） 14-1219/R Primary 4-3-oxosteroid 5β-reductase gene; Cholestasis; Bile acid therapy; Aldo-keto reductase 1D1; Bile acid synthetic defects ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 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. 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 |
| ISSN: | 1007-9327 2219-2840 2219-2840 |
| DOI: | 10.3748/wjg.v18.i47.7113 |