title: Molecular analysis of CYP21A2 can optimize the follow-up of positive results in newborn screening for congenital adrenal hyperplasia.
abstract: Neonatal screening for congenital adrenal hyperplasia (CAH) is useful in diagnosing salt wasting form (SW). However, there are difficulties in interpreting positive results in asymptomatic newborns. The main objective is to analyze genotyping as a confirmatory test in children with neonatal positive results. Patients comprised 23 CAH children and 19 asymptomatic infants with persistently elevated 17-hydroxyprogesterone (17OHP) levels. CYP21A2 gene was sequenced and genotypes were grouped according to the enzymatic activity of the less severe allele: A1 null, A2 < 2%, B 3-7%, C > 20%. Twenty-one children with neonatal symptoms and/or 17OHP levels > 80 ng/ml carried A genotypes, except two virilized girls (17OHP < 50 ng/ml) without CAH genotypes. Patients carrying SW genotypes (A1, A2) and low serum sodium levels presented with neonatal 17OHP > 200 ng/ml. Three asymptomatic boys carried simple virilizing genotypes (A2 and B): in two, the symptoms began at 18 months; another two asymptomatic boys had nonclassical genotypes (C). The remaining 14 patients did not present CAH genotypes, and their 17OHP levels were normalized by 14 months of age. Molecular analysis is useful as a confirmatory test of CAH, mainly in boys. It can predict clinical course, identify false-positives and help distinguish between clinical forms of CAH.
authors.affiliation: Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, CEP 90430.091, Porto Alegre, Rio Grande do Sul, Brazil. bethlsilveira@gmail.com
authors.forename: E L
authors.initials: EL
authors.lastname: Silveira
authors.forename: R H
authors.initials: RH
authors.lastname: Elnecave
authors.forename: E P
authors.initials: EP
authors.lastname: dos Santos
authors.forename: V
authors.initials: V
authors.lastname: Moura
authors.forename: E M
authors.initials: EM
authors.lastname: Pinto
authors.forename: I
authors.initials: I
authors.lastname: van der Linden Nader
authors.forename: B B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: T A S S
authors.initials: TA
authors.lastname: Bachega
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D019326:17-alpha-Hydroxyprogesterone; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase