title: Difficulties in diagnosis and treatment of 5alpha-reductase type 2 deficiency in a newborn with 46,XY DSD.
abstract: OBJECTIVE
  Steroid 5alpha-reductase deficiency (MIM*607306) caused by mutations in the SRD5A2 gene is characterized by a predominantly female phenotype at birth and significant virilization at puberty. The undermasculinization at birth results from low dihydrotestosterone (DHT) levels during fetal development as the type 2 isoenzyme activity is reduced. In puberty, when the type 1 isoenzyme activity increases, significant virilization occurs. Most 46,XY individuals with 5alpha-reductase 2 deficiency develop a male gender identity.
  
  
  RESULTS
  We present a case with a predominantly female phenotype and ambiguous external genitalia but a normal 46,XY karyotype. Plasma steroid analysis after beta-hCG stimulation at 8 days of age revealed a steroid profile estimated as normal with a testosterone (T)/DHT ratio of 9.5 initially misleading to the exclusion of 5alpha-reductase deficiency. However, mutation analysis of the SRD5A2 gene revealed a homozygote point mutation (Leu55Gln) confirming the diagnosis of 5alpha-reductase deficiency. A male phenotype was successfully achieved by hormone treatment with T and DHT after diagnosing 5alpha-reductase deficiency and a masculinization operation. As a side effect skeletal age accelerated temporarily.
  
  
  CONCLUSIONS
  In individuals with predominantly female phenotype and suspected 5alpha-reductase deficiency, a T/DHT ratio during the neonatal period >8.5 might point to 5alpha-reductase deficiency. After confirmation of the diagnosis by molecular analysis of the SRD5A2 gene, a satisfactory change to a male phenotype can be achieved by hormone treatment preceding surgery.
authors.affiliation: Department of Pediatrics and Adolescents Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Kerstin N
authors.initials: KN
authors.lastname: Walter
authors.forename: Frederike B
authors.initials: FB
authors.lastname: Kienzle
authors.forename: Alexander
authors.initials: A
authors.lastname: Frankenschmidt
authors.forename: Olaf
authors.initials: O
authors.lastname: Hiort
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Wudy
authors.forename: Natascha
authors.initials: N
authors.lastname: van der Werf-Grohmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: Karl Otfried
authors.initials: KO
authors.lastname: Schwab
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D013196:Dihydrotestosterone / Q000097:blood*; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000201:enzymology* / Q000235:genetics / Q000601:surgery; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D017354:Point Mutation; D013739:Testosterone / Q000097:blood*
chemical_list: D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase