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Comment & Response |

Does Newborn Screening Have 100% Sensitivity to Detect Salt-Wasting Congenital Adrenal Hyperplasia?  A Word of Caution

Scott D. Grosse, PhD1; Kyriakie Sarafoglou, MD2
[+] Author Affiliations
1National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
2Division of Endocrinology, Department of Pediatrics, University of Minnesota Amplatz Children’s Hospital, Minneapolis
JAMA Pediatr. 2014;168(10):970-971. doi:10.1001/jamapediatrics.2014.1505.
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To the Editor In a recent issue of JAMA Pediatrics, Gidlöf et al1 reported on 26 years of data from the Swedish newborn screening program for congenital adrenal hyperplasia (CAH), more than double the years of any report on CAH screening, to date. In contrast to other CAH newborn screening reports from the United States and Germany,24 Gidlöf et al reported that the rate of detection for salt-wasting (SW)–CAH was 100%. Their assertion that none were missed presumes that none of 39 infants who died after an elevated initial screening test result before confirmatory testing was performed had SW-CAH, which was not shown. The authors compared the median 17α-hydroxyprogesterone values among the 39 infants who died with those of infants possessing the null and I2 splice genotypes for the 21-hydroxylase gene (CYP21A2) to conclude, “In the present study, the 17α-hydroxyprogesterone values were lower in infants with positive screening results who died than the levels detected in infants with the potentially life-threatening salt-wasting form of CAH. This finding suggests that the increased levels of 17α-hydroxyprogesterone were due to nonadrenal disease and that death due to salt-wasting CAH is less likely.”1(p 572-573) However, although the median describes infants in the middle of the distribution, it does not reveal how many of the 39 deceased children might have had 17α-hydroxyprogesterone values consistent with SW-CAH. The authors should have reported the lower-bound 17α-hydroxyprogesterone values for all cases of SW-CAH, not just those with null and I2 splice genotypes, and the numbers of deceased infants who had values higher than the lower bound for infants with confirmed SW-CAH, as was done in a recent UK retrospective screening study.5 To rule out SW-CAH among deceased children with elevated screening values, molecular testing would have to be performed. Consequently, the sensitivity of screening for SW-CAH in Sweden is not known based on 17α-hydroxyprogesterone levels alone. Even the authors admit, “However, because the ranges of 17α-hydroxyprogesterone levels within each genotype group were wide, we could not discriminate between different forms of CAH using the 17α-hydroxyprogesterone values alone.”1 (p 572)


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October 1, 2014
Sebastian Gidlöf, MD, PhD; Anna Nordenström, MD, PhD
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden2Department of Obstetrics and Gynecology, Karolinska University Hospital Huddinge, Stockholm, Sweden
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden3Center for Inherited Metabolic Diseases (CMMS), Karolinska University Hospital, Stockholm, Sweden4Department of Pediatric Endocrinology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital Solna, Stockholm, Sweden
JAMA Pediatr. 2014;168(10):971. doi:10.1001/jamapediatrics.2014.1508.
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