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.

• 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

This study aimed to estimate the number of infants who died of unrecognized congenital adrenal hyperplasia (CAH) in Austria and the Czech Republic within the past 13 years, before the introduction of adequate neonatal screening. The study was based on retrospective analysis of neonatal screening cards of 242 infants who died suddenly between 7 days and 12 months of age and whose cause of death could not be identified. 17-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay and positive samples were subsequently genotyped. Three infants out of 242 may have had unrecognized CAH due to CYP21 (steroid 21-hydroxylase) gene defect. Their newborn 17-OHP levels and CYP21 genotypes were 706 nmol/l and del/conv//del/conv, 53 nmol/l and I2//I2, and 811 nmol/l and I2//Gln318stop, respectively. CAH due to CYP21 defect can lead to sudden unexpected death without prior symptoms typical for the condition. Hence, newborn screening would have prevented these deaths had it been available. In addition, we have shown that the I2 point mutation that is expected to lead to simple virilizing form may lead to a fatal outcome.

• MeSH
• Infant MeSH
• Adrenal Hyperplasia, Congenital epidemiology   MeSH
• Humans MeSH
• Sudden Infant Death epidemiology   MeSH
• Infant, Newborn MeSH
• Neonatal Screening MeSH
• Prevalence MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Austria epidemiology   MeSH