defect in δ-4-3-oxosteroid 5β-reductase

The absence of this cytosolic enzyme results in a lack of the ability to reduce the double bond between C-4 and C-5 of the sterol A-ring, and thus to convert 3-oxo intermediates into the corresponding 3α-hydroxyl products, an essential step in major bile acid synthesis.

This defect results in a markedly reduced primary bile acid synthesis and a concomitant accumulation of δ-4-3-oxo- and allo(5α-H)-bile acids.

A clinical presentation resembling that of neonatal hepatitis is typical, together with rapidly progressive liver disease and liver failure in infancy.

Treatment with bile acid replacement therapy provides beneficial results.