Early Diagnosis of Children with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency by Newborn Screening

Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessively inherited disorders of cortisol biosynthesis in the adrenal cortex. More than 95% are based on a defect in the CYP21A2 gene causing 21-hydroxylase deficiency. Newborn screening (NBS) for CAH by means of 17-hydroxy-progesterone (17-OHP) determination in dried whole blood on filter paper has been introduced as part of the NBS in many countries worldwide. The goals of CAH screening are early detection of the severe, salt-wasting form, therefore prevention of adrenal crisis or death, early detection of the simple virilizing form, and prevention or shortening of the period of incorrect gender assignment in females. Methodological problems of false-positive samples, especially in pre-term infants, can be corrected by adapting the cut-off values for 17-OHP to birth weight, gestational age and age at the time of collection and by performing a second tier screening. Despite a positive voting for newborn CAH screening by the European Society for Pediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society, it is obvious that the acceptance of CAH screening varies worldwide.