Congenital adrenal hyperplasia. Molecular insights learned from patients.

Congenital adrenal hyperplasia (CAH) results from enzymatic blocks in the synthesis of cortisol. All enzyme defects causing CAH are autosomal recessive traits. It is a relatively common disease, occurring in 1 in 5000 to 1 in 15,000 births in most populations. Since the isolation of the gene responsible for steroid 21-hydroxylase deficiency (involved in about 90% of the cases of CAH) in 1984, knowledge of the specific mutations that cause the different forms of CAH has grown rapidly. Mutations in the encoding gene have been confirmed as the basis of endocrine disease in the case of all of the adrenal steroidogenic enzymes required for synthesis of cortisol but one (cholesterol desmolase). The clinical expression of endocrine disease is not always correlated with the mutations of the primary structural gene. Clinicians cannot accurately predict the course of the disease or make therapeutic decisions based on the genotype alone. We will review the various forms of clinical presentation of CAH, their etiology, diagnosis, molecular genetics, and treatment.