Research for the newborn screening system by tandem mass spectrometry

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The usefulness of tandem mass spectometry (TMS) as a new method for newborn screening was investigated in order to improve the prognosis and quality of life of the patients with inherited metabolic disorders in Japan. The blood samples were collected on the fifth or sixth day of life of the newborns, with the informed consent of their parents, in the prefectures of Fukui, Hiroshima and Tokushima, and from selected hospitals in the other areas. We developed a microplate sample process for the measurement of 100,000 samples per year by one TMS instrument using an autoinjector. We analyzed 81,000 newborns and found 4 patients with propionic acidemia and one patient with type II citrullinemia. All of the patients with propionic acidemia are growing uneventfully under the therapies of a protein-restricted diet and carnitine administration.We also analyzed the newborn blood spot s of the patients with such disorders as organic acidemias, disorders of fatty acid oxidation, disorders in carnitine cycle, and disorders in urea cycle. The ratio of propionylcarnitine to acetylcarnitine were shown to be a sensitive marker to identify patients with mild form of propionic acidemia and methylmalonic acidemia. In newborn blood spots of symptomatic patients with fatty acid oxidation disorders, including medium-chai acylCoA dehydrogenase deficiency, acylcarnitine profiles were informative for further diagnostic studies. Citrulline levels were heigher than 1,000 nmo/ml in patients with citrullinemia and lower than 6 nmol/ml in patients with severe forms of ornithine transcarbamylase deficiency.Based on the results in this study, the frequency of the patients with the target disorders in TMS newborn screening in Japan is thought to be more than 1 to 20,000 newborns. We belieave that the nation-wide system of TMS newborn screening should be developed.