CONGENITAL ADRENAL HYPERPLASIA DUE TO 21-HYDROXYLASE DEFICIENCY

Key words: Congenital adrenal hyperplasia, 21-hydroxylase deficiency, Genotype/phenotype correlation, Neonatal screening, Prenatal diagnosis and treatment

Congenital adrenal hyperplasia (CAH) refers to a group of inherited disorders of adrenal steroidogenesis. More than 90% of CAH is due to 21-hydroxylase deficiency (21-OH-D), found in 1:10.000 to 1:15.000 live births as classical form and detected in about 2:100 of certain populations as non classical form. Females with classical 21-OH-D present at birth genital virilization. Potentially life-threatening adrenal crisis may characterize two-third to three-quarters of patients of both sexes with the classical salt wasting (SW) form. Non classical patients may present as precocious pubarche in children or polycystic ovarian syndrome in young women. 21-OH-D is caused by CYP21 gene mutations which in more than 90% of the cases result from inter-genic recombination between the active CYP21 gene and the inactive CYP21P pseudogene. The degree to which each mutation impairs enzymatic activity is strictly correlated with the clinical severity of the disease. Glucocorticoid and mineralcorticoid replacement therapies are the basics of treatment, although alternative strategies of treatment are being developed. Neonatal screening may identify affected children before SW crises develop, reducing mortality of this disease. Prenatal diagnosis and treatment should be performed in families at risk for classical form, underlining them that long term results in dexamethasone treated subjects have however lacking. Long term outcome shows an adult height generally between 1 and 2 standard deviations under the familial target height and a fertility rate only moderately reduced in female more than in male treated patients.