Stable-isotope dilution measurement of isovalerylglycine by tandem mass spectrometry in newborn screening for isovaleric acidemia.
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.
Shigematsu
Yosuke
Y
Department of Health Science, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. yosuke@fmsrsa.fukui-med.ac.jp
Hata
Ikue
I
Tanaka
Yukie
Y
D005189:False Positive Reactions; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood; D045782:Hemiterpenes; D006801:Humans; D007231:Infant, Newborn; D050769:Isovaleryl-CoA Dehydrogenase / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics; D015997:Neonatal Screening / Q000379:methods*; D010421:Pentanoic Acids / Q000097:blood*; D011865:Radioisotope Dilution Technique; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D045782:Hemiterpenes; D010421:Pentanoic Acids; C008216:isovaleric acid; C005916:N-isovalerylglycine; D050769:Isovaleryl-CoA Dehydrogenase; D005998:Glycine