3-beta-hydroxysteroid dehydrogenase (3BHSD) deficiency is a rare genetic disorder in which steroidogenesis is impaired in both the adrenals and the gonads, resulting in decreased production of all three groups of adrenal steroids: mineralocorticoids, glucocorticoids, and sex steroids. The clinical spectrum of this inherited disease is heterogeneous and ranges from a severe salt-wasting form with or without ambiguous genitalia to the non salt-wasting form, with ambiguous genitalia and premature pubarche in young children. Affected neonates exhibit signs and symptoms of adrenal insufficiency of varying degrees. Males tend to show pseudohermaphroditism, while females exhibit normal sexual differentiation or mild virilization. Older females may show hirsutism and/or irregular menstruation.
Until a few years ago elevated ratio of 5-ene-to 4-ene-steroids was considered the best biological parameter for the diagnosis of 3 Beta-HSD Deficiency. However, nowadays plasma levels of 17-OH-pregnenolone greater than 100 nmol/L following ACTH stimulation is considered to be the gold standard for a proper diagnosis of the condition. Patients with the classic form of the condition require treatment with glucocorticoids, mineralocorticoids, and sex steroids. The need for replacement therapy among patients with the late-onset, non-classical form of the condition, varies depending on the severity of the condition.
3-Beta-Hydroxysteroid Dehydrogenase Deficiency is linked to mutations in the HSD3B2 gene. HSD3B2 gene codes for the enzyme beta-hydroxysteroid dehydrogenase that catalyses the oxidation and isomerization of Delta(5)-3beta-hydroxysteroid precursors into Delta(4)-ketosteroids, which is an essential step in the biosynthesis of steroid hormones. In the event of loss of function of this enzyme, the synthesis of all the different classes of hormones is affected.