17-alpha-hydroxylase deficiency, also known as congenital adrenal hyperplasia (CAH) due to 17-alpha-hydroxylase deficiency or congenital adrenal hyperplasia type 5, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the steroidogenesis pathway. It is caused by a mutation in the CYP17A1 gene which encodes the enzyme steroid 17-alpha-hydroxylase. This enzyme hydroxylates both progesterone and pregnenolone into 17-hydroxyprogesterone and 17a-hydroxypregnenolone respectively in the mitochondria, as well as hydroxylating 21-deoxycortisol to 11b-hydroxyprogesterone within the endoplasmic reticulum. When mutated, it leads to an accumulation of pregnenolone, progesterone, deoxycorticosterone and 11-dehydrocorticosterone throughout the cell. 17-alpha hydroxylase deficiency is characterized by a deficiency of sex steroids, as well as glucocorticoids. Symptoms include male undervirilization, as well as lack of development during puberty including amenorrhea for females. Low levels of potassium in the blood due to the increased levels of mineralocorticoids can occur, as well as hypertension. Treatment with dexamethasone has been able to normalize blood pressure and blood potassium levels. It is estimated that 17-alpha-hydroxylase deficiency affects 1 in 1,000,000 individuals.

17-alpha-Hydroxylase Deficiency (CYP17) References

Steroidogenesis References