title: 5α-Reductase-2 Deficiency: Clinical Findings, Endocrine Pitfalls, and Genetic Features in a Large Italian Cohort.
abstract: Clinical records (n = 24) with an established diagnosis of 5α-reductase-2 deficiency were reviewed. A previous misdiagnosis was present in about 70% (period from first observation to definitive diagnosis: 9.1 ± 10.8 years), and in 8 children gonadal removal was performed before certain diagnosis. Initial sex assignment was female in 16/24 (67%) and male in 8/24 (33%) cases. After diagnosis, sex re-assignment was performed in 5 babies (4 girls to male sex; 1 boy to female sex). Baseline testosterone/DHT ratio was diagnostic in 6/12 subjects (first months of life n = 4; puberty n = 2), while post-hCG testosterone/DHT ratio was diagnostic in all tested individuals (choosing both the cut-off value 15 or 10). Eighteen different mutations in the steroid-5α-reductase-2 (SRD5A2) gene were identified, 5 of which have never been reported. In conclusion, a time lag exists before the diagnosis of 5α-reductase-2 deficiency is established; sex assignment and gonadal removal may be performed before certain diagnosis. Sex re-assignment is usually female to male, but the contrary may occur. A large variability in clinical phenotypes and genetic mutations was present in this cohort. Accurate endocrine evaluation is recommended in babies possibly affected by 5α-reductase-2 deficiency, since the use of appropriate cut-off values of testosterone/DHT ratio after hCG stimulation may permit to select individuals for SRD5A2 gene analysis. A genotype-phenotype correlation was not found in this study.
authors.affiliation: Adolescent Medicine, Pediatric Division, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Bertelloni
authors.forename: Fulvia
authors.initials: F
authors.lastname: Baldinotti
authors.forename: Gianni
authors.initials: G
authors.lastname: Russo
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghirri
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dati
authors.forename: Angela
authors.initials: A
authors.lastname: Michelucci
authors.forename: Francesca
authors.initials: F
authors.lastname: Moscuzza
authors.forename: Silvia
authors.initials: S
authors.lastname: Meroni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Colombo
authors.forename: Maria R
authors.initials: MR
authors.lastname: Sessa
authors.forename: Giampiero I
authors.initials: GI
authors.lastname: Baroncelli
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D013196:Dihydrotestosterone / Q000097:blood; D012734:Disorders of Sex Development / Q000097:blood / Q000201:enzymology / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476567:steroid-5alpha-reductase type 2