Isolated mild clitoral hypertrophy may reveal 46,XY disorders of sex development in infancy due to 17betaHSD-3 defect confirmed by molecular analysis.

摘要

AIMS: 17-beta-Hydroxysteroid dehydrogenase type 3 (17betaHSD-3) is expressed exclusively in the testes where it converts Delta4 androstenedione (Delta4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17beta HSD-3 enzyme. METHODS: 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 17betaHSD-3 (HSD17B3) were sequenced. RESULTS: The post-hCG stimulation T levels and T/Delta4 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. CONCLUSIONS: A low T/Delta4 ratio is indicative of 17betaHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17betaHSD-3 deficiency presenting as 46,XY disorder of sex development.