title: Primary ∆4-3-oxosteroid 5β-reductase deficiency: two cases in China.
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.
authors: Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.
authors: Jing
authors: J
authors: Zhao
authors: Ling-Juan
authors: LJ
authors: Fang
authors: Kenneth D R
authors: KD
authors: Setchell
authors: Rui
authors: R
authors: Chen
authors: Li-Ting
authors: LT
authors: Li
authors: Jian-She
authors: JS
authors: Wang
mesh_terms: D001647:Bile Acids and Salts / Q000652:urine; D002681:China; D004252:DNA Mutational Analysis; D005091:Exons; D006529:Hepatomegaly / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism; D008297:Male; D009154:Mutation; D010088:Oxidoreductases / Q000172:deficiency* / Q000235:genetics / Q000652:urine; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid; D010088:Oxidoreductases; C051860:cholestenone 5 beta-reductase
keywords: Aldo-keto reductase 1D1; Bile acid synthetic defects; Bile acid therapy; Cholestasis; Primary ∆4-3-oxosteroid 5β-reductase gene