SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Δ4-steroid 5β-reductase deficiency
Journal
Journal of Gastroenterology and Hepatology (Australia)
Journal Volume
24
Journal Issue
5
Pages
776-785
Date Issued
2009
Author(s)
Ueki I.
Kimura A.
Yorifuji T.
Mori J.
Itoh S.
Maruyama K.
Ishige T.
Takei H.
Nittono H.
Kurosawa T.
Kage M.
Matsuishi T.
Abstract
Background and Aim: We encounter hyper-3-oxo-Δ4 bile aciduria in patients with severe cholestatic liver disease or fulminant liver failure during the neonatal period. However, simply by bile acid analysis, it is difficult to distinguish hyper-3-oxo-Δ4 bile aciduria from primary 3-oxo-Δ4-steroid 5β-reductase deficiency. Methods: To determine whether 3-oxo-Δ4-steroid 5β-reductase (SRD5B1) gene analysis is required for the accurate diagnosis of 3-oxo-Δ4-steroid 5β-reductase deficiency, we evaluated the laboratory data, bile acid analysis and SRD5B1 gene analysis from six patients with hyper-3-oxo-Δ4 bile aciduria. Results: Based upon the results, four patients who had developed neonatal liver failure were diagnosed as having neonatal hemochromatosis. Two patients with chronic cholestasis were diagnosed as having primary 3-oxo-Δ4-steroid 5β-reductase deficiency by SRD5B1 gene analysis. The SRD5B1 gene in these two patients had a heterozygous mutation, G737A (Gly 223 Glu) in one patient and C217T (Arg 50 stop) in the other. Conclusions: Based upon our limited data, we conclude that SDR5B1 gene analysis is required for the accurate diagnosis of 3-oxo-Δ4-steroid 5β-reductase deficiency. Moreover, we think that it is important to elucidate whether there is a heterozygous or a compound heterozygous mutation of the SRD5B1 gene in our two patients. ? 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Subjects
Inborn error of bile acid metabolism; Mutation analysis; Neonatal cholestasis; Ursodeoxycholic acid therapy
SDGs
Other Subjects
3 oxo delta4 steroid 5beta reductase; arginine; chenodeoxycholic acid; disofenin tc 99m; glutamine; glycine; oxidoreductase; unclassified drug; ursodeoxycholic acid; 3 oxo delta4 steroid 5beta reductase deficiency; aciduria; article; bile acid blood level; cholestasis; computer assisted tomography; diagnostic accuracy; enzyme deficiency; female; gallbladder scintiscanning; gene mutation; genetic analysis; hemochromatosis; histopathology; human; human tissue; infant; jaundice; laboratory diagnosis; liver biopsy; liver cirrhosis; liver failure; liver function test; major clinical study; male; newborn; nuclear magnetic resonance imaging; physical examination; priority journal; Autopsy; Bile Acids and Salts; Cholestasis; Diagnosis, Differential; DNA Mutational Analysis; Fatal Outcome; Female; Genetic Testing; Heterozygote; Humans; Infant, Newborn; Japan; Liver; Male; Metabolism, Inborn Errors; Mutation; Oxidoreductases; Phenotype; Predictive Value of Tests; Taiwan; Treatment Outcome
Publisher
Blackwell Publishing
Type
journal article