2007 Fiscal Year Final Research Report Summary
Study of metabolic screening, diagnosis, evaluation of treatment, and molecular analysis for organic and fatty acid disorders
| Project/Area Number |
17390302
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 University |
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Principal Investigator |
YAMAGUCHI Seiji Shimane University, Faculty of Medicine, Professor (60144044)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAO Toshiyuki Gifu University, Graduate School of Medicine, Professor (70260578)
HASEGAWA Yuki Shimane University, Faculty of Medicine, Assistant Professor (00362921)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Organic acidemia / fatty acid disorder / mass spectrometry / fast -GC / MS / enzymatic diaanosis / gene analysis / International cooperation / China. Vietnam. India |
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| Research Abstract |
Metabolic screening, diagnosis, evaluation of clinical course, and molecular analysis on organic and fatty acid disorders were studied, and the following achievements were obtained.
1) Development of the diagnostic support systems for new screening for inherited metabolic disorders of organic and fatty acids: a) A precise method of prenatal diagnosis for organic acid disorders was developed by analysis of amniotic fluid supernatant using two methods, GUMS and Tandem MS, which is very simple and fast; b) The method of enzymatic evaluation of beta-oxidation was developed. The utility of the method was confirmed with analysis of cultured cells from several patients with FAODs.
2) Fast-GUMS method: Fast-GC/MS method, using extremely narrow column was developed. The analytical time was cut down to 1/4 of the conventional GUMS using capillary column.
3) Cell function of cultured fibroblasts from fatty acid oxidation disorders (FAOD): Cells from FAODs patients such as VLCAD deficiency (VLCADD), MCAD deficiency (MCADD), CPU deficiency and glutaric acidemia type 2 (GA2) were cultured in the condition of high temperature, and it was revealed that oxidation of medium chain fatty acids was accelerated, while that of longer chain fatty acids was inhibited. It suggested that FAOD patients potentially have a risk of acute encephalopathy in the febrile condition. On the other hand, metabolic condition of FAOD cells was improved by Bezafibrate, a hypolipidemic drug.
4) Molecular basis of Japanese FAODs: Over 10 Japanese patients with VLCADD and GA2 were analyzed at the molecular levels. Genotypes of these diseases were heterogeneous in Japanese.
5) Study of etiology of diseases and effect of newborn screening using tandem MS: It was suggested that he proportion of diseases between Japanese and the other Asian counties was different. Outcomes between patients detected by newborn screening was much better than those detected after onset stage.
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Research Products
(67 results)
