title: Delayed diagnosis of congenital adrenal hyperplasia with salt wasting due to type II 3beta-hydroxysteroid dehydrogenase deficiency.
abstract: Classical 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3beta-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slight growth acceleration, and advanced bone age, whereas sibling 2 had no signs of virilization. At referral, increased 17alpha-hydroxyprogesterone associated with premature pubarche at first suggested a nonclassical 21-hydroxylase deficiency. Sequencing of the CYP21 gene showed both girls only heterozygotes (V281L mutation). This result, combined with SW in infancy, suggested a 3beta-HSD deficiency because of increased dehydroepiandrosterone sulfate levels. Further hormonal studies showed markedly elevated Delta5-steroids, in particular 17alpha-hydroxypregnenolone greater than 100 nmol/liter (the clue to the diagnosis) and elevated Delta5-/Delta4-steroid ratios. Sequencing of the type II 3beta-HSD gene documented that both girls were compound heterozygotes for T181I and 1105delA mutations. Retrospectively, elevated levels of 17alpha-hydroxyprogesterone were found on blood spots from Guthrie's test. There is no previous report of the combination of SW and premature pubarche due to mutations in the type II 3beta-HSD gene. Because neonatal diagnosis could have prevented life-threatening crises in these girls, this report further supports the benefits for neonatal screening for congenital adrenal hyperplasia whatever the etiology.
authors.affiliation: University Department of Growth and Reproduction, GR-5064, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. trinejohannsen@rh.dk
authors.forename: Trine H
authors.initials: TH
authors.lastname: Johannsen
authors.forename: Delphine
authors.initials: D
authors.lastname: Mallet
authors.forename: Harriet
authors.initials: H
authors.lastname: Dige-Petersen
authors.forename: Jørn
authors.initials: J
authors.lastname: Müller
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.forename: Yves
authors.initials: Y
authors.lastname: Morel
authors.forename: Maguelone G
authors.initials: MG
authors.lastname: Forest
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone; D002648:Child; D002675:Child, Preschool; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007010:Hyponatremia / Q000209:etiology*; D007986:Luteinizing Hormone / Q000097:blood
chemical_list: D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015096:3-Hydroxysteroid Dehydrogenases