21-hydroxylase deficiency

21-hydroxylase deficiency (also known as congenital adrenal hyperplasia) is an inherited disorder that affects the adrenal glands. These glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. Two of these hormones, cortisol and aldosterone, are produced from cholesterol through the activity of an enzyme called 21-hydroxylase. Cortisol has numerous functions such as maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. Aldosterone, sometimes called the salt-retaining hormone, acts on the kidneys to regulate the levels of salt and water in the body, which affects blood pressure. People with 21-hydroxylase deficiency have a shortage of the 21-hydroxylase enzyme, which impairs the conversion of cholesterol to cortisol and aldosterone. When the precursors of cortisol and aldosterone build up in the adrenal glands, they are converted to male sex hormones called androgens. Androgens are normally responsible for the appearance of secondary sex characteristics in males (virilization). Elevated levels of androgens can affect the growth and development of both males and females.

There are three types of 21-hydroxylase deficiency. Two types are classic forms, known as the simple virilizing and salt-loss types. Simple virilizing 21-hydroxylase deficiency causes a buildup of potent androgens that leads to the masculinization (development of male characteristics) of external genitalia in females at birth. The development of the internal reproductive organs (uterus and ovaries) in these patients is normal. Salt-loss 21-hydroxylase deficiency results from an almost complete loss of enzyme activity. In these cases, so little aldosterone is produced that the kidneys do not reabsorb sodium (a component of salt). In the third type of 21-hydroxylase deficiency, known as the nonclassic form, levels of functional 21-hydroxylase enzyme are moderate. Both males and females with the nonclassic type can display signs and symptoms of androgen excess after birth.

The classic form of 21-hydroxylase deficiency appears in 1 in 15,000 newborns. The prevalence of the nonclassic form of 21-hydroxylase deficiency is estimated to be 1 in 100 individuals. The prevalence of both classic and nonclassic forms may vary among different ethnic populations.

Mutations in the CYP21A2 gene cause 21-hydroxylase deficiency.

Mutations in the CYP21A2 gene are often caused by exchanges of DNA between the CYP21A2 gene and a very similar but nonfunctional piece of DNA called a pseudogene. These mutations alter the structure or production of the enzyme and cause 21-hydroxylase deficiency. Generally, mutations that only partially impair enzyme levels or function will have milder effects than more severe mutations that eliminate or greatly reduce the level of 21-hydroxylase enzyme.

Read more about the CYP21A2 gene.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.