4 research outputs found
Metabonomics of Newborn Screening Dried Blood Spot Samples: A Novel Approach in the Screening and Diagnostics of Inborn Errors of Metabolism
A novel, single stage high resolution mass spectrometry-based
method
is presented for the population level screening of inborn errors of
metabolism. The approach proposed here extends traditional electrospray
tandem mass spectrometry screening by introducing nanospray ionization
and high resolution mass spectrometry, allowing the selective detection
of more than 400 individual metabolic constituents of blood including
acylcarnitines, amino acids, organic acids, fatty acids, carbohydrates,
bile acids, and complex lipids. Dried blood spots were extracted using
a methanolic solution of isotope labeled internal standards, and filtered
extracts were electrosprayed using a fully automated chip-based nanospray
ion source in both positive and negative ion mode. Ions were analyzed
using an Orbitrap Fourier transformation mass spectrometer at nominal
mass resolution of 100 000. Individual metabolic constituents
were quantified using standard isotope dilution methods. Concentration
threshold (cutoff) level-based analysis allows the identification
of newborns with metabolic diseases, similarly to the traditional
electrospray tandem mass spectrometry (ESI-MS/MS) method; however,
the detection of additional known biomarkers (e.g., organic acids)
results in improved sensitivity and selectivity. The broad range of
detected analytes allowed the untargeted multivariate statistical
analysis of spectra and identification of additional diseased states,
therapeutic artifacts, and damaged samples, besides the metabolic
disease panel