What causes congenital adrenal hyperplasia?
Congenital adrenal hyperplasia is an inherited disorder. It is a recessive disease, which means that a child must inherit one copy of the defective gene from each parent who is a carrier; when two carriers have children, each pregnancy carries a 25%
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risk of producing an affected child.
In females, congenital adrenal hyperplasia produces an enlarged clitoris at birth and masculinization of features as the child grows, such as deepening of the voice, facial hair, and failure to menstruate or abnormal periods at puberty. Females with severe CAH may be mistaken for males at birth. In males, the genitals are normal at birth, but the child becomes muscular, the penis enlarges, pubic hair appears, and the voice deepens long before normal puberty, sometimes as early as two to three years of age. In the severe salt-wasting form of CAH, newborns may develop symptoms shortly after birth, including vomiting, dehydration, electrolyte (a compound such as sodium or calcium that separates to form ions when dissolved in water) changes, and cardiac arrhythmia.
In the mild form of congenital adrenal hyperplasia, which occurs in late childhood or early adulthood, symptoms include premature development of pubic hair, irregular menstrual periods, unwanted body hair, or severe acne. However, sometimes there are no symptoms.
This particular group of genes contains instructions that the adrenal glands need in order to produce a certain enzyme, 21-hydroxylase (21-OHP). Without this enzyme, the adrenal glands are unable to synthesize cortisol, a hormone necessary for life, in physiologically sufficient amounts.
Cortisol is a steroid produced by the adrenal glands that is needed for our bodies to deal with physical and emotional stress, and to maintain adequate energy supply and blood sugar levels. The adrenal glands are actually controlled by the pituitary gland. The pituitary gland is a small pea-shaped gland at the base of the brain. When the pituitary gland senses that there is not enough cortisol present in the bloodstream, it releases a hormone called ACTH (adrenocoricotrophic hormone). ACTH stimulates the adrenals to produce more cortisol. However, those with CAH have insufficient amounts of the enzyme 21-OHP needed to convert a precursor molecule called 17-hydroxyprogesterone (17-OHP) into cortisol. As a result, the pituitary gland continues to sense the need for cortisol and pumps out more ACTH. This leads to an overabundance of 17-OHP, which is converted in the adrenals into excess androgens, masculinizing steroid hormones. Lack of adequate cortisol also prevents the body from properly metabolizing sugar and responding to stress. The lack of this stress response can lead to drowsiness and possibly coma. |
