| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yasuyuki Gifu University, School of Medicine, Associate Professor, 医学部, 助教授 (00163014)
SAWADA Jun Kyoto Prefectural University of Medicine, Professor, 医学部, 教授 (10079874)
HASHIMOTO Takashi Sinshu University, School of Medicine, Professor, 医学部, 教授 (80009935)
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| Research Abstract |
We have studied on the development of a system for early diagnosis and molecular analysis of mitochondrial and peroxisomal fatty acid beta-oxidation defects (FAOD) in Japan. The results were as follows :
1) In GC/MS analysis of urinary organic acids, acylglycine analysis for the detection of mitochondrial FAOD was established, using stable isotope dilution analysis. Furthermore, it was disclosed that the detection of dicarboxylepoxicides of long-chain carbon length was useful for diagnosis of peroxisomal FAOD.
2) The screening method using blood filter paper was established for the peroxisomal FAOD.
3) Acylcarnitnie analysis by tanden MS for the diagnosis of mitochondrial FAOD was established.
4) Patients with mitochondrial and peroxisomal FAODs diagnosed in Japan were survelyed and investigated. There were 40 and 17 patients with definite mitochondrial and peroxisomal FAODs, respectively.
5) Enzymatic and immunochemical detection for 11 mitochondrial and 10 peroxisomal FAODs was established.
6) Several Japanese patients with novel mitochondrial FAODs, such as very-long chain acyl-CoA dehydrogenase deficiency or trifunctional protein deficiency, were investigated at the molecular levels.
7) A novel peroxisomal enzyme, D-bifunctional protein, was discovered, purified and cloned. Furthermore, a patient with a deficiency of the enzyme was identified, and investigated at the enzymatic and molecular levels.
8) Based on the results of this project, we are intending to develop a system of early diagnosis and molecular analysis for the disorders in this field in Japan. It includes mass spectrometric, enzymatic, immunochemical, and genetic approaches.
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