PRIMARY BILE ACID SYNTHESIS DEFECTS (3β-HYDROXY-Δ5-C27-STEROID DEHYDROGENASE (3β-HSD) DEFICIENCY, OR Δ4-3-OXOSTEROID 5β-REDUCTASE (Δ4-3-OXOR) DEFICIENCY)

These inborn errors of primary bile acid synthesis are rare autosomal recessive cholestatic disorders, leading to inadequate synthesis (or complete absence) of the primary bile acids and resulting in the build-up of atypical and hepatotoxic bile acid intermediates.51

The combined prevalence of 3β-HSD and Δ4-3-oxoR deficiencies is estimated to be 1.13 cases per 10 million.52 Unless patients are treated, chronic liver disease usually progresses to cirrhosis and liver failure before adulthood.51

Diagnosis

3β-HSD or Δ4-3-oxoR deficiency should be suspected in cases of:52

Absence of pruritus, normal serum-GGT activity, and normal or low total serum primary bile acid concentration are common diagnostic features, but specific diagnosis is based on mass spectrometry analysis of urinary bile acids showing typical bile acid profiles with confirmation by gene sequencing.53

Additional disease information can be found in the section BILE ACID SYNTHESIS DISORDERS

51. Gonzales E, Matarazzo L, Franchi-Abella S, et al. Cholic acid for primary bile acid synthesis defects: a life-saving therapy allowing a favorable outcome in adulthood. Orphanet J Rare Dis 2018;13:190.

52. Jahnel J, Zöhrer E, Fischler B, et al. Attempt to determine the prevalence of two inborn errors of primary bile acid synthesis: results of a European survey. J Pediatr Gastroenterol Nutr 2017;64:864-8.

53. Gonzales E, Gerhardt MF, Fabre M, et al. Oral cholic acid for hereditary defects of primary bile acid synthesis: a safe and effective long-term therapy. Gastroenterology 2009;137:1310-20.e13203.