Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: A two-year summary from the New Englandnewborn screening program

Background: Tandem mass spectrometry (MS/MS) is rapidly being adopted by ne wborn screening programs to screen dried blood spots for > 20 markers of di sease in a single assay. Limited information is available for setting the m arker cutoffs and for the resulting positive predictive values. Methods: We screened > 160 000 newborns by MS/MS. The markers were extracte d from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple rea ction monitoring of each sample for the markers of interest was accomplishe d in similar to1.9 min. Cutoffs for each marker were set at 6-13 SD above t he population mean. Results: We identified 22 babies with amino acid disorders (7 phenylketonur ia, 11 hyperphenylalaninemia, 1 maple syrup urine disease, I hypermethionin emia, 1 arginosuccinate lyase deficiency, and 1 argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogen ase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficien cies, 2 propionic acidemias, 1 camitine palmitoyltransferase 11 deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long c hain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcamitine markers; appro ximately one-half of all the flagged infants were from the 5% of newborns w ho required neonatal intensive care or had birth weights < 1500 g. Conclusions: In screening for 23 metabolic disorders by MS/MS, an mean posi tive predictive value of 8% can be achieved when using cutoffs for individu al markers determined empirically on newborns. (C) 2001 American Associatio n for Clinical Chemistry.