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

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...

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Bibliographic Details
Published in:	Clinical genetics Vol. 76; no. 6; pp. 503 - 510
Main Authors:	Silveira, EL, Elnecave, RH, Dos Santos, EP, Moura, V, Pinto, EM, Van Der Linden Nader, I, Mendonca, BB, Bachega, TASS
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-12-2009 Wiley-Blackwell
Subjects:	17-alpha-Hydroxyprogesterone - blood 17OHP level 21-hydroxylase deficiency Adrenal Hyperplasia, Congenital - blood Adrenal Hyperplasia, Congenital - diagnosis Adrenal Hyperplasia, Congenital - enzymology Adrenals. Adrenal axis. Renin-angiotensin system (diseases) Biological and medical sciences Child Child, Preschool congenital adrenal hyperplasia CYP21A2 mutations Endocrinopathies Female Follow-Up Studies Fundamental and applied biological sciences. Psychology General aspects. Genetic counseling Genes Genetics of eukaryotes. Biological and molecular evolution Heterozygote Humans Infant Infant, Newborn Male Medical genetics Medical sciences Medical screening Molecular and cellular biology Neonatal care Neonatal Screening newborn screening Non tumoral diseases. Target tissue resistance. Benign neoplasms Steroid 21-Hydroxylase - genetics Endocrinopathy Human 21-hydroxylase deficiency Adrenal cortex diseases Enzyme Deficiency Hydroxylase Hyperadrenocorticism Medical screening CYP21 A2 mutations Enzymopathy congenital adrenal hyperplasia Congenital adrenal hyperplasia syndrome 170HP level Screening Newborn Follow up study Newborn animal Adrenal gland diseases Genetics Oxidoreductases Mutation newborn screening
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Summary:	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.
Bibliography:	ark:/67375/WNG-SBJDRVJT-5 istex:04BF4D8B49E86385A5D83E7512E2BE0C18CAB981 ArticleID:CGE1274 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-9163 1399-0004
DOI:	10.1111/j.1399-0004.2009.01274.x