Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment.

Abstract

BACKGROUND AND AIMS:

In two Japanese infants with neonatal cholestasis, 3-oxo-Δ(4)-steroid 5β-reductase deficiency was diagnosed based on mutations of the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Δ(4) bile acids were detected in their serum and urine by gas chromatography-mass spectrometry. We studied effects of oral chenodeoxycholic acid treatment.

PATIENTS AND METHODS:

SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and treatment of these two patients were investigated retrospectively and prospectively investigated.

RESULTS:

With respect to SRD5B1, one patient was heterozygous (R266Q, a novel mutation) while the other was a compound heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in improving liver function and decreasing unusual bile acids such as 7α-hydroxy- and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine.

CONCLUSION:

Primary bile acid treatment using chenodeoxycholic acid was effective for these patients treated in early infancy before the late stage of chronic cholestatic liver dysfunction.

• Authors: Yoshitaka Seki, Tatsuki Mizuochi, Akihiko Kimura, Tomoyuki Takahashi, Akira Ohtake, Shin-Ichi Hayashi, Toshiya Morimura, Yasuharu Ohno, Takayuki Hoshina, Kenji Ihara, Hajime Takei, Hiroshi Nittono, Takao Kurosawa, Keiko Homma, Tomonobu Hasegawa, Toyojiro Matsuishi
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 36 Issue 3 Pg. 565-73 (May 2013) ISSN: 1573-2665 [Electronic] United States
• PMID: 23160874 (Publication Type: Case Reports, Journal Article)

Chemical References

• Bile Acids and Salts
• Gastrointestinal Agents
• Chenodeoxycholic Acid
• Oxidoreductases
• 3-oxo-5 beta-steroid delta 4-dehydrogenase

Topics

• Asian People
• Bile Acids and Salts (metabolism)
• Chenodeoxycholic Acid (therapeutic use)
• Cholestasis (diagnosis, drug therapy, genetics, metabolism)
• Female
• Gastrointestinal Agents (therapeutic use)
• Humans
• Infant, Newborn
• Infant, Newborn, Diseases (diagnosis, drug therapy, genetics, metabolism)
• Liver (drug effects, metabolism, pathology)
• Male
• Mutation (physiology)
• Oxidoreductases (genetics)