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

UMMS Affiliation

Department of Pediatrics; New England Newborn Screening Program

Publication Date


Document Type



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.

Journal/Book/Conference Title

Clinical chemistry

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