Congenital adrenal hyperplasia (CAH) is a group of genetic disorders affecting the adrenal glands, which regulate hormone production in the body.
CYP21A2-related or 21-hydroxylase-deficient (OHD CAH) causes insufficient 21-hydroxylase enzyme production. This enzyme deficiency leads to hormone imbalances, including an excess of androgens. Classic 21-OHD CAH has two severe subtypes: salt wasting and simple virilizing. Salt wasting CAH, with near-complete enzyme deficiency, can cause severe dehydration, vomiting, diarrhea, and even death if untreated. It often leads to ambiguous genitalia in females and enlarged genitals in males. Simple virilizing CAH, with partial enzyme deficiency, doesn’t typically cause life-threatening symptoms but leads to ambiguous genitalia in most females and signs of early puberty in both sexes.
Non-classic or late-onset CAH is the mildest form, resulting from mild enzyme deficiency. Symptoms may appear in childhood, adolescence, or adulthood, including rapid growth in childhood, shorter stature in adulthood, virilization, and infertility in both genders. Some individuals with non-classic CAH may have such mild symptoms that they remain unaware of the condition.
This form of CAH is caused by pathogenic (disease-causing) variants in the CYP21A2 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Other names for this condition are congenital adrenal hyperplasia 1, congenital adrenal hyperplasia due to 21 hydroxylase deficiency, and CYP21 deficiency.