Which are the causes of Congenital Adrenal Hyperplasia (CAH)?

Congenital Adrenal Hyperplasia (CAH) is a genetic disorder that affects the adrenal glands, which are responsible for producing essential hormones in the body. This condition is caused by a deficiency in certain enzymes that are necessary for the production of these hormones. The most common cause of CAH is a mutation in the gene that codes for the enzymes involved in the synthesis of cortisol, a hormone that helps regulate metabolism, blood pressure, and the immune system.

There are several types of CAH, each caused by a different enzyme deficiency:

1. 21-Hydroxylase Deficiency: This is the most common form of CAH, accounting for about 95% of cases. It is caused by a mutation in the CYP21A2 gene, which leads to a deficiency in the enzyme 21-hydroxylase. This enzyme is responsible for converting hormones called progestins into cortisol and aldosterone. Without enough 21-hydroxylase, the body produces excess androgens (male sex hormones) instead, leading to the development of male characteristics in both males and females.



2. 11-Beta Hydroxylase Deficiency: This type of CAH is caused by a mutation in the CYP11B1 gene, resulting in a deficiency of the enzyme 11-beta hydroxylase. This enzyme is involved in the production of cortisol and aldosterone. Without enough 11-beta hydroxylase, the body accumulates excess progestins, leading to an overproduction of androgens and the development of male characteristics.



3. 17-Alpha Hydroxylase Deficiency: This form of CAH is caused by a mutation in the CYP17A1 gene, which leads to a deficiency in the enzyme 17-alpha hydroxylase. This enzyme is responsible for converting progestins into cortisol and androgens into estrogens. Without enough 17-alpha hydroxylase, the body cannot produce enough cortisol and androgens, resulting in a decrease in male characteristics and an increase in female characteristics.

CAH is an autosomal recessive disorder, meaning that both parents must carry a copy of the mutated gene for their child to be affected. If both parents are carriers, there is a 25% chance with each pregnancy that their child will have CAH, a 50% chance that the child will be a carrier like the parents, and a 25% chance that the child will not inherit the mutated gene.

It is important to note that CAH is not caused by anything the parents did or did not do during pregnancy. It is purely a genetic condition that is present from birth. However, certain populations may have a higher prevalence of CAH due to a higher carrier rate of the mutated genes.

The symptoms and severity of CAH can vary depending on the specific enzyme deficiency and the level of hormone imbalance. Common symptoms include ambiguous genitalia in females, early development of male characteristics in both males and females, salt-wasting (a condition where the body loses too much salt), and hormonal imbalances that can affect growth and development.

Early diagnosis and treatment are crucial in managing CAH. Treatment typically involves hormone replacement therapy to restore the balance of hormones in the body. This may include medications to replace cortisol and aldosterone, as well as suppress the overproduction of androgens. Regular monitoring and follow-up with healthcare professionals are essential to ensure optimal management of the condition.