The molecular and clinical spectrum of 3beta-hydroxysteroid dehydrogenase deficiency disorder.

Severe 3beta-hydroxysteroid dehydrogenase (3beta-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 Delta5 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 3beta-HSD deficiency CAH. Recent studies of the type II 3beta-HSD gene encoding adrenal and gonadal 3beta-HSD have indicated that only the severe 3beta-HSD deficiency CAH results from a deleterious mutation in the gene. This indicates that the mild Delta5 steroid abnormality is not due to a variant of 3beta-HSD deficiency CAH. The hormonal criteria for bona fide mild variants of 3beta-HSD deficiency and etiology of mild Delta5 steroid abnormality in the patients remain to be investigated.