Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program
Department of Pediatrics; New England Newborn Screening Program
Amino Acid Metabolism, Inborn Errors; Blood Specimen Collection; Carboxylic Acids; Fatty Acids; Humans; Infant, Newborn; Lipid Metabolism, Inborn Errors; Mass Spectrometry; Massachusetts; Neonatal Screening; Predictive Value of Tests
Genetics and Genomics | Life Sciences | Medical Genetics | Medicine and Health Sciences | Pediatrics
BACKGROUND: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values.
METHODS: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in approximately 1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean.
RESULTS: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g.
CONCLUSIONS: In screening for 23 metabolic disorders by MS>/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.
Clin Chem. 2001 Nov;47(11):1945-55.
Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, Shih VE, Johnson DM, Strauss AW, Comeau AM, Eaton RB, Grady GF. (2001). Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. Open Access Articles. Retrieved from https://escholarship.umassmed.edu/oapubs/463