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Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Endocr Rev. 2000 Jun; 21(3):245-91.ER

Abstract

More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21-hydroxylase deficiency. Females with severe, classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilized external genitalia. Most patients cannot synthesize sufficient aldosterone to maintain sodium balance and may develop potentially fatal "salt wasting" crises if not treated. The disease is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombinations between CYP21 and the closely linked CYP21P pseudogene. Approximately 20% are gene deletions due to unequal crossing over during meiosis, whereas the remainder are gene conversions--transfers to CYP21 of deleterious mutations normally present in CYP21P. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disease in patients carrying it. Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition. Glucocorticoid and mineralocorticoid replacement are the mainstays of treatment, but more rational dosing and additional therapies are being developed.

Authors+Show Affiliations

Division of Pediatric Endocrinology, University of Texas Southwestern Medical Center, Dallas 75390-9063, USA. pwhit2@mednet.swmed.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

10857554

Citation

White, P C., and P W. Speiser. "Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency." Endocrine Reviews, vol. 21, no. 3, 2000, pp. 245-91.
White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21(3):245-91.
White, P. C., & Speiser, P. W. (2000). Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocrine Reviews, 21(3), 245-91.
White PC, Speiser PW. Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency. Endocr Rev. 2000;21(3):245-91. PubMed PMID: 10857554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. AU - White,P C, AU - Speiser,P W, PY - 2000/6/17/pubmed PY - 2000/10/14/medline PY - 2000/6/17/entrez SP - 245 EP - 91 JF - Endocrine reviews JO - Endocr Rev VL - 21 IS - 3 N2 - More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21-hydroxylase deficiency. Females with severe, classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilized external genitalia. Most patients cannot synthesize sufficient aldosterone to maintain sodium balance and may develop potentially fatal "salt wasting" crises if not treated. The disease is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombinations between CYP21 and the closely linked CYP21P pseudogene. Approximately 20% are gene deletions due to unequal crossing over during meiosis, whereas the remainder are gene conversions--transfers to CYP21 of deleterious mutations normally present in CYP21P. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disease in patients carrying it. Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition. Glucocorticoid and mineralocorticoid replacement are the mainstays of treatment, but more rational dosing and additional therapies are being developed. SN - 0163-769X UR - https://www.unboundmedicine.com/medline/citation/10857554/Congenital_adrenal_hyperplasia_due_to_21_hydroxylase_deficiency_ L2 - https://academic.oup.com/edrv/article-lookup/doi/10.1210/edrv.21.3.0398 DB - PRIME DP - Unbound Medicine ER -