What is 21-hydroxylase deficiency?
The inherited condition 21-hydroxylase deficiency (also known as congenital adrenal hyperplasia) is a disorder of steroid metabolism (the production or breakdown of steroids). Steroids are types of lipids (fats) that include cholesterol, vitamin D, and many hormones. People with a shortage of the enzyme 21-hydroxylase cannot convert cholesterol to cortisol and aldosterone, steroid hormones that regulate stress responses and blood pressure, respectively. When the precursors of cortisol and aldosterone build up in the adrenal glands (small glands attached to the kidneys), they are converted to male sex hormones called androgens. 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 reproductive organs (uterus and ovaries) in these patients is normal. Salt-loss 21-hydroxylase deficiency results from an extremely severe loss of enzyme activity. In these cases, so little aldosterone is produced that the kidneys do not reabsorb sodium (in the form of salt). In the third type of 21-hydroxylase deficiency, known as the nonclassic form, there are moderate levels of functional 21-hydroxylase enzyme. Both males and females with the nonclassic type can display signs and symptoms of androgen excess after birth.
How common is 21-hydroxylase deficiency?
The incidence of the classic forms of 21-hydroxylase deficiency is 1 in 15,000 live births. 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 in some ethnic populations.
What genes are related to 21-hydroxylase deficiency?
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.
How do people inherit 21-hydroxylase deficiency?
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
What other names do people use for 21-hydroxylase deficiency?
- Adrenogenital Syndrome
- Congenital Adrenal Hyperplasia
- Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency