Congenital adrenal hyperplasia: 21-hydroxylase deficiency in the newborn and during infancy

Congenital adrenal hyperplasia is a family of monogenic autosomal recessive disorders of steroidogenesis with protean clinical manifestations. The commonest form, 21-hydroxylase deficiency, is the most frequent cause of ambiguous genitalia in the newborn. The molecular features associated with abnormalities in the CYP21 gene are well characterized in relation to phenotypic manifestations. The concordance between genotype and phenotype is sufficiently robust as to be relevant and useful in planning treatment strategies. Thus, the dose of glucocorticoid replacement in the early years of life can be tailored according to the predicted degree of 21-hydroxylase enzyme deficiency in the anticipation that this may avoid hitherto excessive steroid replacement during the critical early years of growth and development. The means to prevent genital virilization in affected females is clearly demonstrated by the success of early dexamethasone administration to pregnant mothers at risk. Short-term outcome studies of children exposed to dexamethasone in utero indicate no significant adverse effects. Nevertheless, it is recommended that prenatal treatment programs to prevent a major congenital malformation of the urogenital system be conducted only as part of agreed national multicenter studies, which include a commitment to long-term outcome analyses.