Context: Congenital adrenal hyperplasia (CAH) is a common monogenic recessive disorder. It has been suggested that CYP21A2 deficiency is common because carriers may have a survival advantage, 1 in 15,000 in most populations. Carriers of CYP21A2 mutations typically do not have clinical symptoms but have a defined phenotype with a more prompt cortisol response to ACTH. Objective: We investigated whether the mortality was lower, and determined the cause of death in carriers and population controls. Design: A total of 1143 obligate carriers of a CYP21A2 mutation (561 men) were identified from the Swedish National CAH Registry, encompassing >700 patients and the Multi-Generation Registry to identify their parents. The mortality and cause of death were identified through the Swedish Cause of Death Registry. The hazard ratios (HRs) and 95% CIs were calculated. The results were compared with controls from the general population, matched for sex and age. Results: The overall mortality was lower in carriers of a CYP21A2 mutation compared with the controls (HR 0.79; 95% CI, 0.678 to 0.917; P = 0.002). The difference was more marked among carriers of a more severe mutation. Infection as the cause of death was significantly lower (HR 0.65; 95% CI, 0.48 to 0.87; P < 0.01), particularly for death in pneumonia (HR 0.22; 95% CI, 0.06 to 0.88; P = 0.03). The lower overall mortality among women compared with men in the general population was confirmed among both carriers and controls. Conclusion: Obligate CYP21A2 carriers of a classic mutation had a reduced mortality. Specifically, a possible reduced mortality due to pneumonia was seen.
CITATION STYLE
Nordenström, A., Svensson, J., Lajic, S., Frisén, L., Nordenskjöld, A., Norrby, C., … Falhammar, H. (2019). Carriers of a Classic CYP21A2 Mutation Have Reduced Mortality: A Population-Based National Cohort Study. Journal of Clinical Endocrinology and Metabolism, 104(12), 6148–6154. https://doi.org/10.1210/jc.2019-01199
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