17β-Hydroxysteroid dehydrogenase III deficiency

17-beta hydroxysteroid dehydrogenase 3 deficiency is a rare inherited condition that disrupts male sexual development. Affected people are genetically male, with one X and one Y chromosome and testes, but the testes make too little testosterone because a variant of the HSD17B3 gene leaves the enzyme that converts androstenedione to testosterone with little or no activity. Before birth the shortage of testosterone prevents the external sex organs from forming in the usual male pattern, so most affected infants have genitalia that look female, some look ambiguous, and some look mostly male with a small penis or hypospadias. At puberty other tissues produce more testosterone and male secondary sex characteristics appear, sometimes with breast enlargement, although affected people are generally infertile. The condition is inherited in an autosomal recessive pattern and occurs in about 1 in 147,000 newborns, far more often among the Arab population of Gaza.