Context: The late presentation of steroid 5a-reductase-2 (SRD5A2) deficiency in females is poorly characterised. The ratios of 5a/5b-reduced metabolites of adrenal steroids in a urine steroid profile (USP) can give an indication of SRD5A2 deficiency, although the diagnostic cut-off for 5a/5b ratios are not clearly defined in genetically confirmed cases. Objective: The aim of this study was to establish the frequency of SRD5A2 deficiency in an adult clinic for disorders of sexual development (DSD) focussing on 46XY partially virilised adult female subjects. We investigated the relationship between USP results and SRD5A2 genetic sequence and determined the cut-off for USP 5a/5b-reduced steroid ratios compared with gene sequencing for the identification of SRD5A2 deficiency. Methods: USP and SRD5A2 genetic analyses were performed in 23 adult females, aged 19-57 years, with 46XY DSD and in four males with confirmed SRD5A2 deficiency. 5a-Reductase activity was assessed using the USP ratio of androsterone to aetiocholanolone (A/Ae), 5a-tetrahydrocortisol (5a-THF)/tetrahydrocortisol (THF) and 5a-tetrahydrocorticosterone to tetrahydrocorticosterone (5a-THB/THB). Results: The SRD5A2 gene mutations were found in 10/23 (43%) females and in all four males. Totally, four novel mutations were identified. All mutation-positive subjects had A/Ae and 5a-THB/THB ratios below the lower limit of normal (100% sensitivity) while the sensitivity of 5a-THF/THF ratio was 90%. Conclusion: SRD5A2 deficiency is more prevalent than expected in the adult female 46XY DSD population. The clinical spectrum of this disorder may extend to a more female phenotype than previously considered to include individuals with little or no virilisation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.