A False Negative Case with 21-Hydroxylase Deficiency at Newborn Mass Screening Program

--- Case Report and Review of the Mass Screening Program in Kagoshima Prefecture ---

Abstract

We report the first case with 21-hydroxylase deficiency (21-OHD) not detected by the newborn mass screening program in Kagoshima prefecture. A one year and four months old girl was referred to the Kagoshima University Hospital because of her ambiguous genitalia. Her plasma level of ACTH and serum level of 17α-hydroxyprogesterone (17-OHP) were extremely high at her initial consultation, although at the time of newborn mass screening her paper disk blood 17-OHP was 5.8 ng/ml which was less than the cut-off point (7 ng/ml) used in the mass screening. The diagnosis of 21-OHD was confirmed by gene analysis of the steroid 21-hydroxylase gene (CYP21B). The patient had I172N (exon4) and R356W (exon8) heterozygous variations. We reviewed the screening program in Kagoshima prefecture because of this false negative case. Although the incidence of false negative cases is rare, this case informs that normal results at screening cannot exclude the possibility of congenital adrenal hyperplasia.