General Medical Information

3b-Hydroxysteroid Dehydrogenase

Joe Leigh Simpson

This enzyme deficiency is inherited in autosomal recessive fashion. Decreased synthesis of both androgens and estrogens occurs . The major androgen produced is DHEA, as already discussed. DHEA is a weaker androgen than testosterone and as such is not capable of adequately virilizing the male fetus. Diagnosis usually is established on the basis of serum DHEA levels before and after ACTH stimulation. In addition to genital abnormalities, 3b-ol-dehydrogenase deficiency is associated with severe sodium wasting, given that both aldosterone and cortisol are decreased.

Incompletely developed external genitalia of males with 3b-hydroxysteroid dehydrogenase (3b-HSD) deficiency are clinically similar to the external genitalia of most other male pseudohermaphrodites: small phallus, urethral opening proximal on the penis, and incomplete labioscrotal fusion. Testes and wolffian ducts differentiate normally. Given that affected females (46,XX) also show genital ambiguity, 3b-ol-dehydrogenase (3b-HSD) is the only enzyme that, when deficient, produces male pseudohermaphroditism in males and female pseudohermaphroditism in females.

3b-HSD is a microsomal enzyme, unlike 21-hydroxylase or 11b-hydroxylase. The gene is located on 1p13.1. Type I is expressed in placenta, skin, and breasts; type II is expressed in adrenal cortex and gonads. Male pseudohermaphroditism results from type II mutations, usually due to point mutations.