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Genotyping Is a Valuable Diagnostic Complement to Neonatal Screening for Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency¹

Department of Pediatrics (A.N., A.L.) and PKU Screening Laboratory (A.N., L.H.A.L.), Huddinge University Hospital, Karolinska Institute, S-141 86 Huddinge, Sweden; the Department of Pediatrics, Ryhov (A.T.), S-551 85 Jökoping, Sweden; and the Department of Molecular Medicine, CMM:02, Karolinska Hospital (A.W.), S-171 76 Stockholm, Sweden

Address all correspondence and requests for reprints to: Anna Nordenström, M.D., Department of Pediatrics, Huddinge University Hospital, Karolinska Institute, S-141 86 Huddinge, Sweden.

To evaluate genotyping as a diagnostic complement to neonatal screening for congenital adrenal hyperplasia, 91 children who had been diagnosed with this condition between 1986 and 1997 were analyzed for mutations in the steroid 21-hydroxylase gene. Screening levels of 17-hydroxyprogesterone were compared in patients representing different genotypes. Genotyping was performed using allele-specific PCR, the patients were divided into four groups according to the severity of their mutations, and screening results were compared between these groups as well as with 141 values representing false positive samples. The screening levels of 17-hydroxyprogesterone were significantly different in the five groups of samples. Values above 500 nmol/L were clearly associated with the most severe genotypes, whereas conclusions concerning disease severity could not be drawn from individual samples representing lower levels. For example, values around 150–200 nmol/L could be seen in children with all degrees of disease severity and could also constitute false positive samples. We conclude that genotyping is a valuable diagnostic tool and a good complement to neonatal screening, especially in confirming or discarding the diagnosis in cases with slightly elevated 17-hydroxyprogesterone levels. An additional benefit is that it provides information on disease severity, which reduces the risk of overtreatment of mildly affected children.

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