Minu M George, Sunil Sinha, Irene Mamkin+6 more · 2011 · Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · added 2026-04-24
17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation Show more
17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17β HSD-3 enzyme. We describe a 3-year old healthy female of consanguineous Lebanese descent, who presented to the endocrine service with isolated mild clitoromegaly. Adrenocorticotropic hormone (ACTH) and human chorionic gonadotrophin (hCG) stimulation tests were performed. Genes for sex-determining region Y (SRY), steroidogenic factor-1 (SF-1) and 17βHSD-3 (HSD17B3) were sequenced. The post-hCG stimulation T levels and T/Δ4 ratio was low. Patient had a 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a homozygous R80W missense mutation on exon 3. No mutation was found in SRY and SF1 genes. Mullerian structures were not detected on pelvic imaging. A low T/Δ4 ratio is indicative of 17βHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17βHSD-3 deficiency presenting as 46,XY disorder of sex development. Show less
17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) deficiency is a rare, but frequently misdiagnosed autosomal recessive cause of 46,XY disorder of sex development (DSD). 17βHSD-3 enzyme is present a Show more
17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) deficiency is a rare, but frequently misdiagnosed autosomal recessive cause of 46,XY disorder of sex development (DSD). 17βHSD-3 enzyme is present almost exclusively in the testes and converts Δ4-androstenedione (Δ4) to testosterone (T). The diagnosis can be easily missed in early childhood as the clinical presentation may be subtle. Any young girl with an inguinal hernia, mild clitoromegaly, single urethral opening or urogenital sinus should raise suspicion. If not diagnosed early, patients present with severe virilization and primary amenorrhea in adolescence and may undergo a change from a female to male gender role. A low T/Δ4 ratio on baseline or hCG (human chorionic gonadotropin)-stimulated testing is suggestive of 17βHSD-3 deficiency. The diagnosis can be confirmed with molecular genetic studies. This review summarizes the clinical presentations, reported mutations, diagnosis, treatment and clinical course of this disorder. The Arg80 site in exon 3 is the most common location of repeated mutations and can be considered a hot spot in certain Arab populations. Show less