3?-hydroxysteroid dehydrogenase type II deficiency on newborn screening test

Abstract

SUMMARY3b-hydroxysteroid dehydrogenase II (3b-HSD) deficiency represents a rare CAH variant. Newborns affected with its classic form have salt wasting in early infancy and genital ambiguity in both sexes. High levels of 17-hydroxypregnenolone (Δ 5 17OHP) are characteristic, but extra-adrenal conversion to 17-hydroxyprogesterone (17OHP) may lead to positive results on newborn screening tests. Filter paper 17OHP on newborn screening test was performed by immunofluorometric assay, and serum determinations of 17OHP and Δ 5 17OHP, by radioimmunoassay. A 46,XY infant with genital ambiguity and adrenal crisis at three months of age presented a positive result on newborn screening for CAH. Serum determinations of 17OHP and Δ 5 17OHP were elevated, and a high Δ 5 17OHP/cortisol relation was compatible with the diagnosis of 3b-HSD deficiency. Molecular analysis of the HSD3B2 gene from the affected case revealed the presence of the homozygous p.P222Q mutation, whereas his parents were heterozygous for it. We present the first report of 3b-HSD type II deficiency genotype-proven detected at the Newborn Screening Program in Brazil. The case described herein corroborates the strong genotypephenotype correlation associated with the HSD3B2 p.P222Q mutation, which leads to a classic salt-wasting 3b-HSD deficiency. Further evaluation of 17OHP assays used in newborn screening tests would aid in determining their reproducibility, as well as the potential significance of moderately elevated 17OHP levels as an early indicator to the diagnosis of other forms of classic CAH, beyond 21-hydroxylase deficiency. Arq Bras Endocrinol Metab. 2014;58(6):650-5 SUMÁRIO A deficiência da enzima 3b-hidroxiesteroide desidrogenase tipo 2 (3b-HSD) representa variante rara de hiperplasia adrenal congenital (HAC). Recém-nascidos afetados com a forma clássi-ca apresentam perda de sal nas primeiras semanas de vida e ambiguidade genital em ambos os sexos. Concentrações elevadas de 17-hidroxipregnenolona (Δ 5 17OHP) são características, porém sua conversão extra-adrenal a 17-hidroxiprogesterona (17OHP) pode resultar em resultados positivos no teste de triagem neonatal. A determinação da concentração de 17OHP obtida em amostra de sangue colhida em papel-filtro para triagem neonatal foi realizada por ensaio imunofluorimétrico, e as concentrações séricas de 17OHP and Δ 5 17OHP, por radioimunoensaio. Um menino, 46,XY, com ambiguidade genital e crise adrenal aos 3 meses de vida, apresentou teste positivo na triagem neonatal para HAC. As concentrações séricas de 17OHP e Δ 5 17OHP estavam aumentadas, bem como a relação Δ 5 17OHP/cortisol, o que foi compatível com o diagnóstico de deficiência de 3b-HSD. A análise molecular do gene HSD3B2 revelou a mutação p.P222Q em homozigose na criança afetada e em heterozigose em seus pais, o que confirmou a deficiência de 3b-HSD com resultado moderadamente elevado na dosagem de 17OHP no "Teste do Pezinho" (Programa de Triagem Neonatal do Distrito Federal, Brasil). Esse caso corrobora a forte correlação genótipo-fenótipo associad...

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study with 38,935 Infants

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