The Molecular and Clinical Spectrum of 3β-hydroxysteroid Dehydrogenase Deficiency Disorder

Abstract

Severe 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency in the adrenals and gonads is a well known cause of salt-wasting and non-salt-wasting forms of congenital adrenal hyperplasia (CAH), male pseudohermaphroditism and mild androgen excess symptoms in children and older females. A mild spectrum of Δ5 steroid abnormality in young children with premature pubarche and older females with hirsutism and menstrual disorder was presumed to be due to a mild variant of 3β-HSD deficiency CAH. Recent studies of the type II 3β-HSD gene encoding adrenal and gonadal 3β-HSD have indicated that only the severe 3β-HSD deficiency CAH results from a deleterious mutation in the gene. This indicates that the mild Δ5 steroid abnormality is not due to a variant of 3β-HSD deficiency CAH. The hormonal criteria for bona fide mild variants of 3β-HSD deficiency and etiology of mild Δ5 steroid abnormality in the patients remain to be investigated.