The progression to 21-hydroxylase deficiency usually involves the defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol which results in decreased cortisol synthesis and therefore increased corticotropin (ACTH) secretion. The resulting adrenal stimulation leads to increased production of androgens due to shunting of the pathway to androgen synthesis. More than 95% of cases of congenital adrenal hyperplasia (CAH) are caused by 21-hydroxylase deficiency. The clinical manifestations of congenital adrenal hyperplasia is closely related to the type and severity of disease. The severity of disease relates to the type of mutation which causes enzyme inactivity or hypo-activity. There is a lack of enzyme in classic form of 21-hydroxylase deficiency; while in the non-classic form, enzymatic activity is reduced but sufficient to maintain normal glucocorticoid and mineralocorticoid production. The gene responsible for 21-hydroxylase deficiency is CYP21A. This gene is located within the human leucocyte antigen class III region of chromosome 6. Meiotic recombination occurs in this genomic region as a result of the high degree of sequence homology between CYP21A2 and its pseudogene CYP21A1. Approximately 70% of CYP21A2 genetic mutation is due to gene conversion and micro-deletions in CYP21A1 gene.
21-hydroxylase deficiency pathophysiology
21-hydroxylase deficiency causes
21-hydroxylase deficiency risk factors
11β-hydroxylase deficiency risk factors
Lipoid congenital adrenal hyperplasia pathophysiology
17 alpha-hydroxylase deficiency risk factors
5-alpha-reductase deficiency pathophysiology
21-hydroxylase deficiency laboratory findings