Prenatal diagnosis and treatment of congenital adrenal hyperplasia owing to 21-hydroxylase deficiency

Classical forms of congenital adrenal hyperplasia are caused by a severe deficiency of 21-hydroxylase, an enzyme involved in steroid biosynthesis, which triggers excessive androgen production before birth. Affected females experience virilization both physically and psychologically. Prenatal diagnosis and treatment of congenital adrenal hyperplasia has been implemented for more than 20 years. In utero gene-specific diagnosis is now feasible for fetal cell samples derived from chorionic villi or amniotic cells in culture, and this gene-specific diagnosis guides the treatment of the affected female fetus. Appropriate dexamethasone administration to the at-risk pregnant mother is effective in reducing genital virilization in the fetus, and thus avoids unnecessary genitoplasty in affected females. Current data from large human studies show the benefit and safety of prenatal treatment. Long-term follow-up of the safety of prenatal treatment is currently underway. This practice is a rare example of effective prenatal treatment to prevent a malformation caused by an inborn error of metabolism.