Molecular analysis of CYP21A2 can optimize the follow-up of positive results in newborn screening for congenital adrenal hyperplasia

Autor(es)

Silveira, E. L. ^[1] ; Elnecave, R. H. ^[1] ; dos Santos, E. P. ^[2] ; Moura, V. ^[2] ; Pinto, E. M. ^[3] ; Nader, I. van der Linden ^[2] ; Mendonca, B. B. ^[3] ; Bachega, T. A. S. S. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Rio Grande do Sul, Serv Endocrinol, Hosp Clin Porto Alegre, Porto Alegre, RS - Brazil

^[2] Programa Estadual Triagem Neonatal Goias, Lab APAE Anapolis, Anapolis, Go - Brazil

^[3] Univ Sao Paulo, Lab Hormonios & Genet Mol LIM42, Disciplina Endocrinol, Hosp Clin, Fac Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Genetics; v. 76, n. 6, p. 503-510, DEC 2009.
• Citações Web of Science: 15

Resumo

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. (AU)

• Processo FAPESP: 06/56532-7 - Incidencia da deficiencia de 21-hidroxilase e frequencia das mutacoes no gene cyp21a2 no programa de triagem neonatal de goias.
• Beneficiário: Tania Aparecida Sartori Sanchez Bachega
• Linha de fomento: Auxílio à Pesquisa - Regular