Which enzyme deficiency leads to congenital adrenal hyperplasia?

Congenital adrenal hyperplasia (CAH) primarily results from a deficiency in the enzyme 21-hydroxylase. This enzyme is crucial in the steroidogenesis pathway, where it catalyzes the conversion of 17-hydroxyprogesterone and progesterone into corticosteroids and mineralocorticoids. When there is a deficiency of 21-hydroxylase, the pathway is blocked, leading to the accumulation of steroid precursors, primarily 17-hydroxyprogesterone.

This deficiency causes a decrease in cortisol and aldosterone production, which results in an adrenal insufficiency state. As a compensatory mechanism, the pituitary gland secretes increased levels of adrenocorticotropic hormone (ACTH) due to low cortisol levels, leading to further stimulation of the adrenal cortex and hyperplasia of the adrenal glands. The imbalance in adrenal steroid production also leads to increased androgen levels, causing various degrees of virilization in affected females and accelerated puberty in males.

The other enzyme deficiencies mentioned may also lead to adrenal dysfunction, but they result in different clinical presentations and biochemical abnormalities. For example, 11-hydroxylase deficiency leads to excess androgens and mineralocorticoid precursors, which