Lessons learned from 5 years of newborn screening for congenital adrenal hyperplasia in the Czech Republic: 17-hydroxyprogesterone, genotypes, and screening performance
Language English Country Germany Media print-electronic
Document type Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- 17-alpha-Hydroxyprogesterone blood MeSH
- Biomarkers blood MeSH
- False Positive Reactions MeSH
- Genetic Markers MeSH
- Genotype MeSH
- Adrenal Hyperplasia, Congenital blood diagnosis genetics MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Neonatal Screening methods MeSH
- Prospective Studies MeSH
- Retrospective Studies MeSH
- Sensitivity and Specificity MeSH
- Steroid 21-Hydroxylase genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- 17-alpha-Hydroxyprogesterone MeSH
- Biomarkers MeSH
- CYP21A2 protein, human MeSH Browser
- Genetic Markers MeSH
- Steroid 21-Hydroxylase MeSH
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.
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