The biochemical basis for genotyping 21-hydroxylase deficiency

We describe three different forms of 21-hydroxylase deficiency-classical congenital adrenal hyperplasia (CAH), late-onset 21-hydroxylase deficiency, and cryptic 21-hydroxylase deficiency-and we present hormonal standards by which to assign the appropriate 21-hydroxylase deficiency genotype for these disorders. The late-onset and cryptic forms of 21-hydroxylase deficiency are biochemically indistinguishable, although patients with the late-onset disorder present with marked clinical symptoms (e.g. virilization) whereas patients with cryptic 21-hydroxylase deficiency are clinically asymptomatic. Our latest studies suggest that late-onset 21-hydroxylase deficiency, like the classical and cryptic 21-hydroxylase deficiencies, is also genetically linked to HLA, the major histocompatibility complex of man. Our biochemical findings provide evidence that a spectrum of 21-hydroxylase deficiencies exist in the population.