Stable-isotope dilution measurement of isovalerylglycine by tandem mass spectrometry in newborn screening for isovaleric acidemia

Clin Chim Acta. 2007 Nov-Dec;386(1-2):82-6. doi: 10.1016/j.cca.2007.08.003. Epub 2007 Aug 19.

Abstract

Background: Recent neonatal screening for isovaleric acidemia by tandem mass spectrometry based on dried blood-spot levels of C5-acylcarnitines, including isovalerylcarnitine and its isomer, pivaloylcarnitine, which is derived from pivalate-generating antibiotics, has caused many false-positive results. We have developed a method to overcome this interference.

Methods: The amounts of isovalerylglycine were determined by a stable-isotope dilution electrospray tandem mass spectrometric analysis, using multiple-reaction monitoring with product ions of m/z 132, which were generated predominantly from quasi-molecular ions of isovalerylglycine butylester but apparently not from those of pivaloylglycine butylester.

Results: Isovalerylglycine concentrations in dried blood spots of control newborns were 0.17+/-0.03 nmol/ml, and those of patients with isovaleric acidemia ranged from 1.3 to 80.0 nmol/ml. Those of the newborns treated with antibiotics, which caused high C5-acylcarnitine levels (1.9+/-1.7 nmol/ml) in dried blood spots, were 0.22+/-0.05 nmol/ml.

Conclusions: Our data showed that the present method is useful in eliminating the false-positive results due to antibiotics use in newborn screening for isovaleric acidemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • False Positive Reactions
  • Glycine / analogs & derivatives*
  • Glycine / blood
  • Hemiterpenes
  • Humans
  • Infant, Newborn
  • Isovaleryl-CoA Dehydrogenase / blood*
  • Isovaleryl-CoA Dehydrogenase / deficiency
  • Isovaleryl-CoA Dehydrogenase / genetics
  • Metabolism, Inborn Errors / diagnosis*
  • Metabolism, Inborn Errors / genetics
  • Neonatal Screening / methods*
  • Pentanoic Acids / blood*
  • Radioisotope Dilution Technique*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*

Substances

  • Hemiterpenes
  • Pentanoic Acids
  • isovaleric acid
  • N-isovalerylglycine
  • Isovaleryl-CoA Dehydrogenase
  • Glycine