SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Δ4-steroid 5β-reductase deficiency

• Published in: Journal of gastroenterology and hepatology 2009-05, Vol.24 (5), p.776-785
• Main Authors: Ueki, Isao, Kimura, Akihiko, Chen, Huey-Ling, Yorifuji, Tohru, Mori, Jun, Itoh, Susumu, Maruyama, Kenichi, Ishige, Takashi, Takei, Hajime, Nittono, Hiroshi, Kurosawa, Takao, Kage, Masayoshi, Matsuishi, Toyojiro
• Format: Article
• Language: English
• Subjects: 3-oxo-Δ4 bile aciduria; Biological and medical sciences; Gastroenterology. Liver. Pancreas. Abdomen; inborn error of bile acid metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; mutation analysis; neonatal cholestasis; Other diseases. Semiology; ursodeoxycholic acid therapy
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2008.05669.x

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.