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

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.