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Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5beta-reductase, in hepatitis and liver failure

H A Lemonde1, E J Custard, J Bouquet

  • 1Biochemistry, Endocrinology, and Metabolism Unit, Institute of Child Health, University College London with Great Ormond Street Hospital for Children NHS Trust, London, UK.

Gut
|September 13, 2003
PubMed

Insights

Genetic 5beta-reductase deficiency was identified in three infants with cholestatic liver disease due to SRD5B1 gene mutations. Early diagnosis and treatment with chenodeoxycholic acid and cholic acid can improve outcomes.

Area of Science:

  • Genetics
  • Biochemistry
  • Hepatology

Background:

  • Infantile cholestatic liver disease can present with unique urinary bile acid profiles.
  • delta(4)-3-oxosteroid 5beta-reductase (SRD5B1) deficiency is a proposed cause for specific bile acid abnormalities.

Observation:

  • Three infants with neonatal cholestatic liver disease exhibited elevated urinary 3-oxo-delta(4) bile acids and low saturated bile acids.
  • These patients lacked normal plasma and urinary levels of chenodeoxycholic acid and cholic acid.

Findings:

  • Mutations in the SRD5B1 gene were identified in all three studied patients.
  • Specific mutations included homozygous missense and frameshift mutations leading to Pro198Leu, premature stop codon, and Leu106Phe substitutions.
  • Liver biopsies revealed giant cell hepatitis and extramedullary hematopoiesis.

Implications:

  • SRD5B1 mutation analysis is crucial for diagnosing genetic 5beta-reductase deficiency.
  • Early treatment with chenodeoxycholic acid and cholic acid can be effective if liver disease is not advanced.
  • Distinguishing genetic deficiency from other causes of bile aciduria is vital for appropriate management.
Abstract

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