Development of a system for early diagnosis and molecular analysis of mitochondrial and peroxisomal fatty acid beta-oxidation defects in Japan.

在日本开发了线粒体和过氧化物酶体脂肪酸β-氧化缺陷的早期诊断和分子分析系统。

基本信息

批准号：
08307008
负责人：
YAMAGUCHI Seiji
金额：
$ 2.3万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

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.

我们在日本研究了线粒体和过氧化物酶体脂肪酸β-氧化缺陷（FAOD）早期诊断和分子分析系统的开发。结果如下：1)在尿有机酸GC/MS分析中，采用稳定同位素稀释分析法，建立了用于检测线粒体FAOD的酰基甘氨酸分析方法。此外，还公开了长链碳长度的二羧氧杀剂的检测对于过氧化物酶体FAOD的诊断有用。2)建立了过氧化物酶体FAOD的血液滤纸筛查方法。3)通过tanden MS进行酰基肉碱分析用于诊断4)对日本确诊的线粒体和过氧化物酶体FAOD患者进行了调查研究。分别有 40 名和 17 名患者患有明确的线粒体和过氧化物酶体FAOD。5) 建立了对 11 种线粒体和 10 种过氧化物酶体FAOD 的酶法和免疫化学检测。6) 几名日本患者患有新型线粒体FAOD，例如极长链酰基辅酶A脱氢酶缺陷或三功能蛋白缺陷，在分子水平上进行了研究。 7) 一种新型过氧化物酶体酶，D-双功能蛋白，被发现、纯化和克隆的。此外，还确定了一名缺乏酶的患者，并在酶和分子水平上进行了研究。8) 根据该项目的结果，我们打算开发一种针对该疾病的早期诊断和分子分析系统。日本的领域。它包括质谱、酶促、免疫化学和遗传方法。