Congenital adrenal hyperplasia (CAH) encompasses a group of genetic disorders that affect the adrenal glands’ ability to produce certain hormones. CAH is primarily caused by mutations in genes involved in the production of enzymes required for the synthesis of cortisol, aldosterone, and other steroid hormones. The specific type of CAH depends on which enzyme is affected. Here are the most common types:
1. 21-Hydroxylase Deficiency (Classic CAH): This is the most common form of CAH, accounting for about 95% of cases. It is caused by mutations in the CYP21A2 gene, which leads to a deficiency in the enzyme 21-hydroxylase. This enzyme is responsible for converting hormones into cortisol and aldosterone. Classic CAH can be further classified into the salt-wasting type, in which aldosterone production is severely impaired, and the simple virilizing type, which primarily affects cortisol production.
2. 11-Beta Hydroxylase Deficiency: This type of CAH is caused by mutations 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. 11-Beta hydroxylase deficiency can lead to excessive production of androgens, causing virilization in females and early puberty in both sexes.
3. 17-Hydroxylase Deficiency: This type of CAH is caused by mutations in the CYP17A1 gene, resulting in a deficiency of the enzyme 17-hydroxylase. This enzyme is involved in the production of cortisol, aldosterone, and sex hormones. 17-Hydroxylase deficiency can lead to a decrease in cortisol and aldosterone production, as well as the accumulation of certain hormones, causing hypertension and the development of ambiguous genitalia in females.
4. Other Rare Forms: There are several other rare forms of CAH caused by mutations in genes involved in adrenal hormone synthesis, such as 3-beta hydroxysteroid dehydrogenase (3BHSD) deficiency, cholesterol side-chain cleavage enzyme (P450scc) deficiency, and others. These forms of CAH have distinct clinical presentations and hormone abnormalities.
The symptoms of congenital adrenal hyperplasia (CAH) can vary depending on the specific type of CAH and the severity of hormone deficiency. Here are some common symptoms associated with different forms of CAH:
1. 21-Hydroxylase Deficiency (Classic CAH):
– Salt-Wasting Type: Newborns with the salt-wasting type may experience dehydration, vomiting, poor feeding, weight loss, low blood pressure, and electrolyte imbalances (such as low sodium levels).
– Simple Virilizing Type: This form of CAH primarily affects cortisol production, leading to symptoms such as early growth of pubic and underarm hair in both males and females, rapid growth during childhood, early onset of puberty, and irregular menstrual periods in females.
2. 11-Beta Hydroxylase Deficiency:
– Excessive production of androgens can cause virilization in females, leading to the development of masculine features such as deepening of the voice, excessive facial and body hair growth, and an enlarged clitoris.
– In both sexes, early puberty, accelerated growth, and high blood pressure may also occur.
3. 17-Hydroxylase Deficiency:
– Decreased production of cortisol and aldosterone can lead to symptoms such as fatigue, weakness, low blood pressure, and salt cravings.
– In females, the deficiency can result in ambiguous genitalia at birth, delayed puberty, and the absence of menstrual periods.
– In males, the deficiency can cause delayed puberty and infertility due to impaired sperm production.
It’s worth noting that the symptoms of CAH can manifest differently in each individual, and some individuals may have milder or atypical presentations. Additionally, CAH may be detected during prenatal screening, leading to early intervention and management.
If you suspect that you or your child may have CAH or are experiencing related symptoms, it’s important to consult with a healthcare professional, such as an endocrinologist or geneticist, for a proper diagnosis and appropriate management. Early detection and treatment can help prevent complications and optimize overall health and well-being.