title: Isolated mild clitoral hypertrophy may reveal 46,XY disorders of sex development in infancy due to 17βHSD-3 defect confirmed by molecular analysis.
abstract: OBJECTIVE
  17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17β 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 17βHSD-3 (HSD17B3) were sequenced.
  
  
  RESULTS
  The post-hCG stimulation T levels and T/Δ4 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/Δ4 ratio is indicative of 17βHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17βHSD-3 deficiency presenting as 46,XY disorder of sex development.
authors.affiliation: Pediatric Endocrinology Division, Maimonides Infants and Children's Hospital and Children's Hospital at SUNY Downstate, Brooklyn, NY, USA.
authors.forename: Minu M
authors.initials: MM
authors.lastname: George
authors.forename: Sunil
authors.initials: S
authors.lastname: Sinha
authors.forename: Irene
authors.initials: I
authors.lastname: Mamkin
authors.forename: Pascal
authors.initials: P
authors.lastname: Philibert
authors.forename: Maria I
authors.initials: MI
authors.lastname: New
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wilson
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ten
authors.forename: Amrit
authors.initials: A
authors.lastname: Bhangoo
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D002675:Child, Preschool; D002987:Clitoris / Q000473:pathology*; D003937:Diagnosis, Differential; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics*; D005260:Female; D006801:Humans; D006984:Hypertrophy; D009154:Mutation; D014770:Virilism
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3