Journal article
Misclassification of VLCAD carriers due to variable confirmatory testing after a positive NBS result
Journal of community genetics, Vol.10(4), pp.447-451
10/01/2019
DOI: 10.1007/s12687-019-00409-8
PMCID: PMC6754489
PMID: 30721391
Abstract
The Iowa Newborn Screening (NBS) Program began screening for very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) in 2003. Untreated VLCAD can lead to liver failure, heart failure, and death. Current confirmatory testing recommendations by the American College of Medical Genetics (ACMG) for VLCAD list molecular and functional analysis (i.e., fibroblast fatty acid oxidation probe) as optional. This can lead to misclassification of VLCAD carriers as false positives. Iowa implemented a comprehensive VLCAD confirmatory testing algorithm at the beginning of 2016 that included both molecular and fibroblast analysis. Here, we compare the historic multi-algorithmic confirmatory testing protocol (2005-2016) to this comprehensive protocol (2016-2017). A metabolic specialist reviewed all medical records and NBS data for each out-of-range VLCAD that fell in each testing period. During the comprehensive testing period, 48,651 specimens were screened. Thirteen individuals with out-of-range C14:1 results were classified as follows after review: ten carriers, zero true positives, zero false positives, zero lost to follow-up, and four unable to assess carrier status. During the variable testing period, a total of 486,566 specimens were screened. Eighty-five individuals with out-of-range C14:1 were classified as follows: 45 carriers, two true positives, four false positives, four lost to follow-up, and 30 unable to assess carrier status. Our findings suggest that many out-of-range VLCAD cases that do not receive molecular confirmatory testing could be carriers mistakenly classified as false positives. We recommend comprehensive molecular and functional testing for all children with out-of-range VLCAD NBS results.
Details
- Title: Subtitle
- Misclassification of VLCAD carriers due to variable confirmatory testing after a positive NBS result
- Creators
- Anne E. Atkins - Center for Translational Research, Children’s National Health System, Washington, USABeth A. Tarini - Center for Translational Research, Children’s National Health System, Washington, USAEmily K. Phillips - University of Iowa Hospitals and ClinicsAmy R. U. L. Calhoun - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of community genetics, Vol.10(4), pp.447-451
- DOI
- 10.1007/s12687-019-00409-8
- PMID
- 30721391
- PMCID
- PMC6754489
- NLM abbreviation
- J Community Genet
- ISSN
- 1868-310X
- eISSN
- 1868-6001
- Publisher
- Springer Nature
- Number of pages
- 5
- Grant note
- Iowa Ladies Football Academy Stead Family Department of Pediatrics University of Iowa Hospital and Clinics
- Language
- English
- Date published
- 10/01/2019
- Academic Unit
- Stead Family Department of Pediatrics; Hygienic Laboratory - Bdc; Medical Genetics and Genomics; Nursing
- Record Identifier
- 9984353799002771
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