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

J Inherit Metab Dis. 2013 May;36(3):565-73. doi: 10.1007/s10545-012-9526-6. Epub 2012 Nov 16.

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.

Publication types

  • Case Reports

MeSH terms

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

Substances

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