Congenital Adrenal Hyperplasia

This chapter discusses congenital adrenal hyperplasia (CAH). It is a group of autosomal recessive disorders that impair normal steroid synthesis due to genetic enzyme deficiencies. The synthesis of cortisol in the adrenal cortex occurs in five major enzyme-mediated steps and deficiency in one of these gives rise to CAH and the most common form is 21-hydroxylase deficiency (21-OHD). The impaired enzyme function during the biosynthesis lead to an increase in precursors and deficient products and results in a chronic elevation of ACTH. Congenial adrenal hyperplasia due to 21-OHD is divided into classical and non-classical forms, with patients of the classical form having more severs symptoms of hyperandrogenism including virilization of the female genitalia. The genetic pathophysiology of the CAH is described with occurrence of more than 100 mutations including point mutations, small deletions, small insertions and complex rearrangements of the gene CYP21A2. The molecular genetic testing of the CYP21A2 gene for a panel of common mutations and gene deletions detects about 80-98% of the disease-causing alleles in the patient.