Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency

Abstract

Type 3 17-beta hydroxysteroid dehydrogenase (17HSD3) deficiency is a rare form of abnormal sex formation (ASF) in 46XY subjects in which the conversion of androstendione to testosterone is blocked; this defect results in compromised masculinization of the external genitalia during the intrauterine development. A distinctive feature of this form of sex development is masculinization at puberty due to the extragonadal conversion of androstendione to testosterone. Two clinical cases are reported: both girls were born with the female-type of external genitalia and 46XY karyotype, but progressive virilization in the pubertal period gave reason to suspect diagnosis of 17HSD3 deficiency. In both cases, this diagnosis was confirmed in molecular genetic studies (the following mutations were identified in the HSD17B3 gene: c.728-734delGATAACCp.1244fsX254/c.277+4A>T and c.277+4A>T). These two cases are the first reports of 17HSD3 deficiency in the Russian literature.