17β-Hydroxysteroid dehydrogenase 3 deficiency

Five known isoenzymes catalyze the 17β-hydroxysteroid dehydrogenase reaction that controls the interconversion of estrone and estradiol and of testosterone and androstenedione. Mutations in the 17β-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with normal male Wolffian duct structures but female external genitalia. Such individuals are usually raised as females but virilize at the time of puberty as the result of a rise in serum testosterone. The 14 mutations characterized to date in 17 affected families include 10 missense mutations, 3 splice junction abnormalities, and 1 frame shift mutation. Three of the mutations have occurred in more than 1 family. The usual mechanism for testosterone formation in affected individuals at puberty appears to be conversion of androstenedione to testosterone in extraglandular tissues by one or more of the unaffected 17β-hydroxysteroid dehydrogenase isoenzymes.