Diagnosis of 17β-hydroxysteroid dehydrogenase deficiency

17β-hydroxysteroid dehydrogenase deficiency is a rare autosomal recessive inherited disorder of sex development, affecting only 46,XY individuals. It is due to mutations in the HSD17B3 gene, encoding the 17β-hydroxysteroid-dehydrogenase type 3 enzyme. Mutated enzymes lead to absent or reduced ability to convert Δ ₄-androstenedione to testosterone in the testis. Affected 46,XY individuals present with testes located in the inguinal canal and underdeveloped or hypoplastic Wolffian structures, but female or ambiguous external genitalia. Such individuals are usually raised as females, but show spontaneous virilization at puberty. Correct diagnosis is mandatory to optimize treatment and follow-up. The clinical and laboratory approach, as well as the follow-up of subjects with 17β-hydroxysteroid-dehydrogenase deficiency, are detailed in this review, and the genetic mutations characterized to date are summarized.