Steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia.

ABSTRACT

Congenital adrenal hyperplasia (CAH) refers to a group of inherited genetic disorders involving deficiencies in enzymes that convert cholesterol to cortisol within the adrenal cortex. There are five key enzymes involved in the production of cortisol. Of these key enzymes, deficiency of 21-hydroxylase is the most commonly defective enzyme leading to CAH representing more than 90% of cases. The low adrenal cortisol levels associated with CAH affects the hypothalamic-pituitary-adrenal negative feedback system leading to increased pituitary adrenocorticotropic hormone (ACTH) production, which overstimulates the adrenal cortex in an attempt to increase cortisol production resulting in a hyperplastic adrenal cortex. The deficiency of enzyme 21-hydroxylase results from mutations or deletions in the CYP21A2 gene found on chromosome 6p. The disorder is transmitted as an autosomal recessive pattern and specific mutations may be correlated to enzymatic compromise of varying degrees, leading to the clinical manifestation of 21-hydroxylase deficiency (21-OHD) CAH.