Effective algorithm to differentiate NBS MCADD cases from carriers and non-carriers and an assessment of the utility of the second newborn screen for MCADD

False positives are an inherent part of newborn screening that can increase both costs to the healthcare system and parental anxiety. Previous studies primarily examined presumptive positive rates for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in places conducting one newborn screen (NBS...

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Published inMolecular genetics and metabolism Vol. 145; no. 4; p. 109183
Main Authors Snyder, Matthew T., Divin, Kristian, Liu, Ning, Sun, Qin, Wang, Yue, Luo, Xi, Ben-Moshe, Yishay, Burrage, Lindsay C., Sutton, V. Reid
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.08.2025
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Online AccessGet full text
ISSN1096-7192
1096-7206
1096-7206
DOI10.1016/j.ymgme.2025.109183

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Abstract False positives are an inherent part of newborn screening that can increase both costs to the healthcare system and parental anxiety. Previous studies primarily examined presumptive positive rates for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in places conducting one newborn screen (NBS), with predominantly white, non-Hispanic subjects. Texas performs two NBSs and there is a majority Hispanic population in our region. This study aims to analyze biochemical and DNA data to more easily distinguish affected individuals from carriers or healthy non-carriers and identify benefits and challenges of a second NBS for MCADD. Biochemical and targeted DNA data from NBS dried blood spots (DBS) were analyzed, alongside diagnostic biochemical and DNA testing. A Kruskal Wallis Test with Dunn's post-test was performed to compare the groups. Significant differences in all analyte values were observed among MCADD, carrier and non-carrier groups, and between carriers and non-p.Lys329Glu homozygous MCADD cases. Many false positives were detected due to low DBS C8 cutoff and the second NBS. An analyte algorithm including DBS C8, plasma acylcarnitine C6, and plasma C8/C10 was identified and discriminated MCADD cases from carrier and non-carrier cases. All cases with MCADD were identified on the first NBS demonstrating limited utility of a second NBS for MCADD.
AbstractList False positives are an inherent part of newborn screening that can increase both costs to the healthcare system and parental anxiety. Previous studies primarily examined presumptive positive rates for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in places conducting one newborn screen (NBS), with predominantly white, non-Hispanic subjects. Texas performs two NBSs and there is a majority Hispanic population in our region. This study aims to analyze biochemical and DNA data to more easily distinguish affected individuals from carriers or healthy non-carriers and identify benefits and challenges of a second NBS for MCADD. Biochemical and targeted DNA data from NBS dried blood spots (DBS) were analyzed, alongside diagnostic biochemical and DNA testing. A Kruskal Wallis Test with Dunn's post-test was performed to compare the groups. Significant differences in all analyte values were observed among MCADD, carrier and non-carrier groups, and between carriers and non-p.Lys329Glu homozygous MCADD cases. Many false positives were detected due to low DBS C8 cutoff and the second NBS. An analyte algorithm including DBS C8, plasma acylcarnitine C6, and plasma C8/C10 was identified and discriminated MCADD cases from carrier and non-carrier cases. All cases with MCADD were identified on the first NBS demonstrating limited utility of a second NBS for MCADD.
False positives are an inherent part of newborn screening that can increase both costs to the healthcare system and parental anxiety. Previous studies primarily examined presumptive positive rates for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in places conducting one newborn screen (NBS), with predominantly white, non-Hispanic subjects. Texas performs two NBSs and there is a majority Hispanic population in our region. This study aims to analyze biochemical and DNA data to more easily distinguish affected individuals from carriers or healthy non-carriers and identify benefits and challenges of a second NBS for MCADD. Biochemical and targeted DNA data from NBS dried blood spots (DBS) were analyzed, alongside diagnostic biochemical and DNA testing. A Kruskal Wallis Test with Dunn's post-test was performed to compare the groups. Significant differences in all analyte values were observed among MCADD, carrier and non-carrier groups, and between carriers and non-p.Lys329Glu homozygous MCADD cases. Many false positives were detected due to low DBS C8 cutoff and the second NBS. An analyte algorithm including DBS C8, plasma acylcarnitine C6, and plasma C8/C10 was identified and discriminated MCADD cases from carrier and non-carrier cases. All cases with MCADD were identified on the first NBS demonstrating limited utility of a second NBS for MCADD.False positives are an inherent part of newborn screening that can increase both costs to the healthcare system and parental anxiety. Previous studies primarily examined presumptive positive rates for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in places conducting one newborn screen (NBS), with predominantly white, non-Hispanic subjects. Texas performs two NBSs and there is a majority Hispanic population in our region. This study aims to analyze biochemical and DNA data to more easily distinguish affected individuals from carriers or healthy non-carriers and identify benefits and challenges of a second NBS for MCADD. Biochemical and targeted DNA data from NBS dried blood spots (DBS) were analyzed, alongside diagnostic biochemical and DNA testing. A Kruskal Wallis Test with Dunn's post-test was performed to compare the groups. Significant differences in all analyte values were observed among MCADD, carrier and non-carrier groups, and between carriers and non-p.Lys329Glu homozygous MCADD cases. Many false positives were detected due to low DBS C8 cutoff and the second NBS. An analyte algorithm including DBS C8, plasma acylcarnitine C6, and plasma C8/C10 was identified and discriminated MCADD cases from carrier and non-carrier cases. All cases with MCADD were identified on the first NBS demonstrating limited utility of a second NBS for MCADD.
ArticleNumber 109183
Author Liu, Ning
Wang, Yue
Divin, Kristian
Ben-Moshe, Yishay
Luo, Xi
Snyder, Matthew T.
Sun, Qin
Burrage, Lindsay C.
Sutton, V. Reid
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Keywords Analyte algorithm
False positive
Newborn screen
Second newborn screen
MCADD
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Snippet False positives are an inherent part of newborn screening that can increase both costs to the healthcare system and parental anxiety. Previous studies...
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SubjectTerms Acyl-CoA Dehydrogenase - blood
Acyl-CoA Dehydrogenase - deficiency
Acyl-CoA Dehydrogenase - genetics
Algorithms
Analyte algorithm
Carnitine - analogs & derivatives
Carnitine - blood
Dried Blood Spot Testing
False positive
False Positive Reactions
Female
Heterozygote
Humans
Infant, Newborn
Lipid Metabolism, Inborn Errors - blood
Lipid Metabolism, Inborn Errors - diagnosis
Lipid Metabolism, Inborn Errors - genetics
Male
MCADD
Neonatal Screening - methods
Newborn screen
Second newborn screen
Title Effective algorithm to differentiate NBS MCADD cases from carriers and non-carriers and an assessment of the utility of the second newborn screen for MCADD
URI https://dx.doi.org/10.1016/j.ymgme.2025.109183
https://www.ncbi.nlm.nih.gov/pubmed/40660651
https://www.proquest.com/docview/3230215191
Volume 145
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