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.

Abstract

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.

• Authors: T H Zytkovicz, E F Fitzgerald, D Marsden, C A Larson, V E Shih, D M Johnson, A W Strauss, A M Comeau, R B Eaton, G F Grady
• Journal: Clinical chemistry (Clin Chem) Vol. 47 Issue 11 Pg. 1945-55 (Nov 2001) ISSN: 0009-9147 [Print] England
• PMID: 11673361 (Publication Type: Journal Article)

Chemical References

• Carboxylic Acids
• Fatty Acids

Topics

• Amino Acid Metabolism, Inborn Errors (diagnosis, epidemiology)
• Blood Specimen Collection (methods)
• Carboxylic Acids (metabolism)
• Fatty Acids (metabolism)
• Humans
• Infant, Newborn
• Lipid Metabolism, Inborn Errors (diagnosis, epidemiology)
• Mass Spectrometry (methods)
• Massachusetts (epidemiology)
• Neonatal Screening (methods)
• Predictive Value of Tests