Genotyping is a valuable diagnostic complement to neonatal screening for congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency

To evaluate genotyping as a diagnostic complement to neonatal screening for congenital adrenal hyperplasia, 91 children who had been diagnosed with th is condition between 1986 and 1997 were analyzed for mutations in the stero id 21-hydroxylase gene. Screening levels of 17-hydroxyprogesterone were com pared in patients representing different genotypes. Genotyping was performe d using allele-specific PCR, the patients were divided into four groups acc ording to the severity of their mutations, and screening results were compa red between these groups as well as with 141 values representing false posi tive samples. The screening levels of 17-hydroxyprogesterone were significa ntly different in the five groups of samples. Values above 500 nmol/L were clearly associated with the most severe genotypes, whereas conclusions conc erning disease severity could not be drawn from individual samples represen ting 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 diagnosti c tool and a good complement to neonatal screening, especially in confirmin g or discarding the diagnosis in cases with slightly elevated 17-hydroxypro gesterone levels. An additional benefit is that it provides information on disease severity, which reduces the risk of overtreatment of mildly affecte d children.