title: Recognition of 5α-reductase-2 deficiency in an adult female 46XY DSD clinic.
abstract: BACKGROUND
  The late presentation of steroid 5α-reductase-2 (SRD5A2) deficiency in females is poorly characterised. The ratios of 5α/5β-reduced metabolites of adrenal steroids in a urine steroid profile (USP) can give an indication of SRD5A2 deficiency, although the diagnostic cut-off for 5α/5β 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 5α/5β-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. 5α-Reductase activity was assessed using the USP ratio of androsterone to aetiocholanolone (A/Ae), 5α-tetrahydrocortisol (5α-THF)/tetrahydrocortisol (THF) and 5α-tetrahydrocorticosterone to tetrahydrocorticosterone (5α-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 5α-THB/THB ratios below the lower limit of normal (100% sensitivity) while the sensitivity of 5α-THF/THF ratio was 90%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, University College London Hospitals, 250 Euston Road, London NW1 2BU, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Berra
authors.forename: Emma L
authors.initials: EL
authors.lastname: Williams
authors.forename: Barbara
authors.initials: B
authors.lastname: Muroni
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Creighton
authors.forename: John W
authors.initials: JW
authors.lastname: Honour
authors.forename: Gill
authors.initials: G
authors.lastname: Rumsby
authors.forename: Gerard S
authors.initials: GS
authors.lastname: Conway
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000328:Adult; D004247:DNA / Q000235:genetics; D058490:Disorder of Sex Development, 46,XY / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005831:Genital Diseases, Female / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007021:Hypospadias / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D020125:Mutation, Missense / Q000502:physiology; D011627:Puberty / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043202:Steroid Metabolism, Inborn Errors; D013256:Steroids / Q000652:urine; D014599:Uterus / Q000002:abnormalities; D014770:Virilism / Q000201:enzymology / Q000235:genetics; D055815:Young Adult
chemical_list: D013256:Steroids; D004247:DNA; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476567:steroid-5alpha-reductase type 2