| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
In order to clarify the accuracy of the methods and the efficacy of the system for newborn screening by tandem mass screening in Japan, a pilot study using the "non-derivatization" methods were performed, and about 50.000 newborns were tested last year. The "non-derivatization" methods had good accuracy and such advantages as safety and rapidness, and were good for large-scaled sample measurements. The isovalerylglycine measurement in dried blood spots (DBS), which was newly developed by us, were useful to eliminate false-positive cases, who were treated pivaloate-generating antibiotics, in isovaleric acidemia screening. A case with short-chain hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency, a rare inherited fatty acid oxidation disorder, was detected using such indices as C4OH-acylcarnitine (C4OH) level and C4OH/C2 ratio. Screening indices for the other fatty acid oxidation disorders were tested, and the necessities of lower cut-off values for the second DBS than the first one, measurements of serum acylcarnitines, and enzyme assays or fatty acid oxidation tests using lymphocytes were suggested. In glutarylcamitine measurements, stable-isotope labeled glutarylcamitine as an internal standard and the instrument with high sensitivity were necessary to perform the accurate measurements. It was indicated that the glutarylcamitine levels were useful to detect SCHAD deficiency as well as glutaric acidemia type I.
The gas chromatograph/mass spectrometric measurements of methylmalonic acid, glutaric acid and 3-hydroxyglutaric acid were performed to evaluate the effects of the therapy for methylmalonic acidemia and glutaric acidemia type I patients. It was shown that the levels of these metabolites, especially in cerebrospinal fluids, were good markers to assess the prognosis for the patients.
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