SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Delta4-steroid 5beta-reductase deficiency.

Abstract

BACKGROUND AND AIM:

We encounter hyper-3-oxo-Delta(4) 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-Delta(4) bile aciduria from primary 3-oxo-Delta(4)-steroid 5beta-reductase deficiency.

METHODS:

To determine whether 3-oxo-Delta(4)-steroid 5beta-reductase (SRD5B1) gene analysis is required for the accurate diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase deficiency, we evaluated the laboratory data, bile acid analysis and SRD5B1 gene analysis from six patients with hyper-3-oxo-Delta(4) 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-Delta(4)-steroid 5beta-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-Delta(4)-steroid 5beta-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.

• Authors: Isao Ueki, Akihiko Kimura, Huey-Ling Chen, Tohru Yorifuji, Jun Mori, Susumu Itoh, Kenichi Maruyama, Takashi Ishige, Hajime Takei, Hiroshi Nittono, Takao Kurosawa, Masayoshi Kage, Toyojiro Matsuishi
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 24 Issue 5 Pg. 776-85 (May 2009) ISSN: 1440-1746 [Electronic] Australia
• PMID: 19175828 (Publication Type: Case Reports, Journal Article, Multicenter Study)

Chemical References

• Bile Acids and Salts
• Oxidoreductases
• cholestenone 5 beta-reductase

Topics

• Autopsy
• Bile Acids and Salts (urine)
• Cholestasis (diagnosis, enzymology, genetics)
• DNA Mutational Analysis
• Diagnosis, Differential
• Fatal Outcome
• Female
• Genetic Testing
• Heterozygote
• Humans
• Infant, Newborn
• Japan
• Liver (enzymology, pathology)
• Male
• Metabolism, Inborn Errors (diagnosis, enzymology, genetics, therapy)
• Mutation
• Oxidoreductases (deficiency, genetics)
• Phenotype
• Predictive Value of Tests
• Taiwan
• Treatment Outcome