| Project/Area Number |
10470178
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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 Medical University |
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Principal Investigator |
YAMAGUCHI Seiji Shimane Medical University, Dept.of Pediatrics, Professor, 医学部, 教授 (60144044)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Naomi Gifu University, Dept.of Pediatrics, Professor, 医学部, 教授 (50124714)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | inborn errors of metabolism / β-oxidation defect / Reye syndrome oxidation / sudden infant death syndrome / fatty acid β-oxidation / molecular analysis / mass spectrometry / グルタル酸尿症2型 / 極長鎖アシル-CoA脱水素酵素欠損症 / 質量分布 / 極長鎖アシル-CoA脱水素酸素欠損症 / 分子生物学 / 脂肪酸代謝異常 |
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| Research Abstract |
Mitochondrial fatty acid beta-oxidation disorders (FAOD) has atracted attention recently. We investigated the acutual situation of Japanese patients with FAOD, and studied the biochemical evaluation and molecular analysis of FAOD patients.
1) Survey of Japanese patients with FAOD : We found 62 Japanese patients with FAOD during the period between 1985 to 2000, using questionnaires, literatures and personal communications. The number of patients was largest in CPT2 deficiency (14), second was glutaric acidemia type 2 (12). The patients in early childhood tend to have acute encephalopathy-like illness, whereas patients in older childhood or adolescence did myopathic illness.
2) Establishment of a simplified GC/MS data processing system : FAOD patients often show nonkletotic dicarboxylic aciduria in organic acidemia screening using GC/MS.We established a personal computer-based system of automated metabolic profiling and diagnosis.
3) Measurement of free fatty acids in dried blood filter paper : For the screening of FAOD, acylcarnitine analysis by tandem MS has become popular. Tandem MS may potentially fail to detect such disorders as a false-negative. We established a simplified, sensitive method to measure the blood free fatty acid levels in blood filter paper.
4) Detection of FAOD by incorporation of RI-labeled fatty acids using cultured cells : We established a screening system for FAOD by incorporation of RI-labeled fatty acids, including palmitate and myristate, analyzing cells from VLCAD deficiency, GA2 and CPT2 deficiency.
5) Molecular analysis of Japanese patients with VLCAD deficiency and GA2 : We identified genetic mutations in five VLCAD deficient patients and three GA2 patients. In VLCAD deficiency, the genotype/phenotype correlation was apparent and the temperature sesitivity was seen among mutations detected. In GA2, we identified the first Japanese case of ETF-alpha subunit deficiency in two patients by pulse labeling and DNA analysis.
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