Genetics of congenital adrenal hyperplasia
Nils Krone, Wiebke Arlt, Nils Krone, Wiebke Arlt
Abstract
Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the deficiency of one of four steroidogenic enzymes involved in cortisol biosynthesis or in the electron donor enzyme P450 oxidoreductase (POR) that serves as electron donor to steroidogenic cytochrome P450 (CYP) type II enzymes. The biochemical and clinical phenotype depends on the specific enzymatic defect and the impairment of specific enzyme activity. Defects of steroid 21-hydroxylase (CYP21A2) and 11beta-hydroxylase (CYP11B1) only affect adrenal steroidogenesis, whereas 17alpha-hydroxylase (CYP17A1) and 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency also impact on gonadal steroid biosynthesis. Inactivating POR gene mutations are the cause of CAH manifesting with apparent combined CYP17A1-CYP21A2 deficiency. P450 oxidoreductase deficiency (ORD) has a complex phenotype including two unique features not observed in any other CAH variant: skeletal malformations and severe genital ambiguity in both sexes.
Conflict of interest statement
DISCLOSURE STATEMENT
The authors report no conflict of interest. This work was supported in part by the Intramural Research Programs of the National Institutes of Health Clinical Center and The Eunice Kennedy Shriver National Institute of Child Health of Human Development (NICHD). All authors have contributed equally to the manuscript. Dr. Merke ensured the scientific integrity of this work.
Figures
Source: PubMed