Newborn screening for medium chain acyl-CoA dehydrogenase deficiency: Performance improvement by monitoring a new ratio

• Published in: Molecular genetics and metabolism 2014-12, Vol.113 (4), p.274-277
• Main Authors: Hall, Patricia L., Wittenauer, Angela, Hagar, Arthur
• Format: Article
• Language: English
• Subjects: Acyl-CoA Dehydrogenase - deficiency; Acyl-CoA Dehydrogenases - genetics; Biomarkers - metabolism; Carnitine - analogs & derivatives; Carnitine - blood; False positive; False Positive Reactions; Heterozygote; Humans; Infant; Infant, Newborn; Infant, Very Low Birth Weight; Lipid Metabolism, Inborn Errors - diagnosis; Lipid Metabolism, Inborn Errors - epidemiology; MCAD deficiency; Medium chain acyl-CoA dehydrogenase; Neonatal Screening - methods; Newborn screening; Performance improvement; United States - epidemiology; Very low birth weight
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2014.10.007

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is a fatty acid oxidation disorder included on newborn screening (NBS) panels in many regions that have expanded to using tandem mass spectrometry for acylcarnitine screening. False positive (FP) screening results for MCAD deficiency have previously been linked to very low birth weight (VLBW) infants and those who are heterozygous for the common mutation, p.K324E. Previous studies have identified these causes of FP screens by sequencing residual dried blood spots. From our cohort of FP screens in Georgia, we identified an elevation at the same mass as octenoylcarnitine (C8:1) causing elevations of octanoylcarnitine (C8) not due to MCAD deficiency. We reviewed biochemical results from 2011 to 2013 for all newborn screens positive for MCAD deficiency in Georgia to identify screening criteria to allow these cases to be identified prospectively, thus saving families the stress of additional testing on their newborn and reducing healthcare costs while improving screening performance for the screening program. We identified the C8/C8:1 ratio as an effective marker, and developed criteria that will reduce FP screening results due to this interfering substance. •We examined false positive newborn screening results for MCAD deficiency.•The majority of false positive screens were from low birth weight infants.•Examining screening results allowed the identification of a ratio to aid in screening.•Utilization of this ratio could improve positive predictive value of MCAD screening.•Fewer false positive screens benefit families, infants, laboratories and providers.