Modifications in electrospray tandem mass spectrometry for a neonatal-screening pilot study in Japan

In a neonatal-screening pilot study for inherited disorders in organic acid and amino acid metabolism, we analyzed butyrated acylcarnitines and amino acids in blood spots of more than 20,000 newborns by electrospray tandem mass spectrometry. In order to screen urea cycle disorders, we performed multiple scanning functions with additional stable isotope-labelled internal standards, since such reported functions as neutral loss of m/z 102 or 109 for butyrated amino acids were not sufficient. Arginine levels were measured with arginine-13C6. Hypocitrullinemia for the screening of some urea cycle disorders was detectable by measurement with synthesized citrulline-d6, although we did not find any such disorders. In the acylcarnitine analysis, we found a patient with propionic acidemia, who has been treated effectively. The increasing false positive rate due to the use of pivalic acid-containing antibiotics in the diagnosis of isovaleric acidemia was a problem in Japan.