Lessons learned from 5 years of newborn screening for congenital adrenal hyperplasia in the Czech Republic: 17-hydroxyprogesterone, genotypes, and screening performance
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Abstract
The aims were to summarize the experience and to determine the performance metrics of newborn screening (NBS) for congenital adrenal hyperplasia (CAH) in the Czech Republic. 17-Hydroxyprogesterone (17OHP) was measured in NBS samples prospectively in 545,026 newborns and retrospectively in 31 CAH patients born outside the study period. A total of 2,811 screened newborns had abnormal 17OHP; CAH was confirmed in 46 probands. One patient with a severe–moderate genotype of CAH had 17OHP below the cut-off and was diagnosed clinically. This corresponds to a screening sensitivity of 98% and a false positive rate (FPR) of 0.51%. The median of 17OHP in the most severe genotypes was 484 nmol/L (n = 21); in severe/moderate, 321 nmol/L (n = 30); in moderate, 61 nmol/L (n = 20); and in mild genotypes, 31 nmol/L (n = 7). NBS is efficient to detect severe CAH but may fail to detect milder variants. However, the FPR is too high but could be improved by application of a second tier test.
Keywords
Newborn screening Congenital adrenal hyperplasia 17-Hydroxyprogesterone CYP21 geneNotes
Acknowledgments
The authors are very grateful to Dr A.M. Wallace, Department of Clinical Biochemistry, Glasgow, Scotland, and Mark McCann, Minnesota Department of Health, St. Paul, Minnesota, USA for 17OHP measurements in NBS samples. The study was supported by the Czech Ministry of Health, project IGA numbers 9981-3 and NT12213 and by the Czech Ministry of Education, project numbers MSM0021620814 and grant numbers MSMT LC06023.
Conflict of interest
The authors declare that they have no conflict of interest.
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