RAPID DIAGNOSIS OF HOMOCYSTINURIA AND OTHER HYPERMETHIONINEMIAS FROM NEWBORNS BLOOD SPOTS BY TANDEM MASS-SPECTROMETRY

We report a new method for the diagnosis of homocystinuria and other h ypermethioninemias from dried blood spots on newborn screening cards, based on isotope-dilution tandem mass spectrometry. The mean concentra tion of methionine in 909 unaffected newborns was 19 mu mol/L (CV 44%) . The variability of results was reduced when the concentration of met hionine was expressed relative to that of another amino acid in the sa me specimen. The mean ratio of methionine to leucine plus isoleucine f or these same newborn blood spots was 0.16 (CV 25%). In newborn sample s from a collection categorized by a Guthrie bacterial inhibition assa y as true positive, unaffected, or falsely positive for hypermethionin emias, the ratio of methionine to leucine for each true-positive speci men was at least 2.5 times greater than for respective age-matched una ffected blood specimens. The ratio for falsely positive samples did no t differ from that for unaffected blood samples. We predict that the r atio of methionine to leucine plus isoleucine determined by tandem mas s spectrometry will successfully detect hypermethioninemias with very low rates for false positives and false negatives.