| Project/Area Number |
10670731
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shimane Medical University |
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Principal Investigator |
KIMURA Masahiko Shimane Medical University, Dept. of Pediatrics, Instructor, 医学部, 講師 (00263533)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Seiji Shimane Medical University, Dept. of Pediatrics, Professor, 医学部, 教授 (60144044)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | glutaric aciduria type 2 / Electron transfer flavoprotein / mitochondrial fatty acid beta oxidation / organic academia |
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| Research Abstract |
Glutaric aciduria type 2 (GA2) is an inherited metabolic disorder of organic acids which is caused by defects of electron transfer flavoprotein (ETF) or ETF dehydrogenase. Due to this defect, several reactions of dehydrogenase and the electron transfer to the respiratory chain are impaired. We studied glutaric aciduria type 2 regarding its screening methods, fatty acid beat oxidation and molecular characterization.
1) As to the screening methods, we developed an automated GC/MS data analysis and diagnosis system of organic acidurias including GA2. Using the system with GD/MS, we established a stable acylglycine analysis for the fatty acid beta-oxidation disorder. Moreover, a free fatty acid analysis using dried blood spots was developed for the screening of the fatty acid beta-oxidation disorder.
2) Fatty acid beta oxidation was evaluated by the production of free water (ィイD13ィエD1HィイD22ィエD2O) from incorporated labeled palmitate and myristate. In GA2, both beta-oxidation of fatty acids were decreased.
3) We newly found two cases of alpha subunit and one case of beta subunit deficiency in Japanese patients. In a pateint with alpha subunit deficiency, confirmed by the pulse-chase experiment, a miss sence mutation of 764G to T (G255V) was found. The other had a compound heterozygosity of 361C to G(P130A) and 799G to A (G267R). In the beta subunit deficiency patient, confirmed by the pulse-chase experiment, we found only a homozygote polymorphism (488C to T) so far.
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