Bile Acid Synthesis Disorders in Japan: Long-Term Outcome and Chenodeoxycholic Acid Treatment

Dig Dis Sci. 2021 Nov;66(11):3885-3892. doi: 10.1007/s10620-020-06722-4. Epub 2021 Jan 1.

Abstract

Background: We encountered 7 Japanese patients with bile acid synthesis disorders (BASD) including 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase (3β-HSD) deficiency (n = 3), Δ4-3-oxosteroid 5β-reductase (5β-reductase) deficiency (n = 3), and oxysterol 7α-hydroxylase deficiency (n = 1) over 21 years between 1996 and 2017.

Aim: We aimed to clarify long-term outcome in the 7 patients with BASD as well as long-term efficacy of chenodeoxycholic acid (CDCA) treatment in the 5 patients with 3β-HSD deficiency or 5β-reductase deficiency.

Methods: Diagnoses were made from bile acid and genetic analyses. Bile acid analysis in serum and urine was performed using gas chromatography-mass spectrometry. Clinical and laboratory findings and bile acid profiles at diagnosis and most recent visit were retrospectively obtained from medical records. Long-term outcome included follow-up duration, treatments, growth, education/employment, complications of treatment, and other problems.

Results: Medians with ranges of current patient ages and duration of CDCA treatment are 10 years (8 to 43) and 10 years (8 to 21), respectively. All 7 patients, who had homozygous or compound heterozygous mutations in the HSD3B7, SRD5B1, or CYP7B1 gene, are currently in good health without liver dysfunction. In the 5 patients with CDCA treatment, hepatic function gradually improved following initiation. No adverse effects were noted.

Conclusions: We concluded that CDCA treatment is effective in 3β-HSD deficiency and 5β-reductase deficiency, as cholic acid has been in other countries. BASD carry a good prognosis following early diagnosis and initiation of long-term CDCA treatment.

Keywords: Bile acid analysis; Bile acid synthesis disorders; CYP7B1; Chenodeoxycholic acid treatment; HSD3B7; SRD5B1.

MeSH terms

  • Adolescent
  • Adrenal Hyperplasia, Congenital / drug therapy*
  • Adrenal Hyperplasia, Congenital / genetics*
  • Adult
  • Bile Acids and Salts / biosynthesis*
  • Chenodeoxycholic Acid / therapeutic use*
  • Child
  • Cytochrome P450 Family 7 / genetics
  • Cytochrome P450 Family 7 / metabolism*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Genetic Predisposition to Disease
  • Humans
  • Japan
  • Mutation
  • Oxidoreductases / genetics*
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism*
  • Young Adult

Substances

  • Bile Acids and Salts
  • Chenodeoxycholic Acid
  • Oxidoreductases
  • Steroid Hydroxylases
  • Cytochrome P450 Family 7
  • CYP7B1 protein, human
  • 3-oxo-5 beta-steroid delta 4-dehydrogenase

Supplementary concepts

  • Adrenal hyperplasia 2