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.
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.
Zytkovicz
T H
TH
New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain, 305 South St., Jamaica Plain, MA 02130, USA. thomas.zytkovicz@state.ma.us
Fitzgerald
E F
EF
Marsden
D
D
Larson
C A
CA
Shih
V E
VE
Johnson
D M
DM
Strauss
A W
AW
Comeau
A M
AM
Eaton
R B
RB
Grady
G F
GF
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology*; D001800:Blood Specimen Collection / Q000379:methods; D002264:Carboxylic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology*; D013058:Mass Spectrometry / Q000379:methods; D008404:Massachusetts / Q000453:epidemiology; D015997:Neonatal Screening / Q000379:methods*; D011237:Predictive Value of Tests
D002264:Carboxylic Acids; D005227:Fatty Acids