胸苷磷酸化酶
线粒体脑肌病
生物
粒线体疾病
线粒体DNA
眼阻
遗传学
线粒体肌病
共济失调
基因
癌症
神经科学
作者
Michio Hirano,Yutaka Nishigaki,Ramón Martí
出处
期刊:The Neurologist
[Lippincott Williams & Wilkins]
日期:2004-01-01
卷期号:10 (1): 8-17
被引量:176
标识
DOI:10.1097/01.nrl.0000106919.06469.04
摘要
Background Mitochondrial encephalomyopathies are clinically and genetically heterogeneous because mitochondria are the products of 2 genomes: mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Among the mendelian-inherited mitochondrial diseases are defects of intergenomic communication, disorders due to nDNA mutations that cause depletion and multiple deletions of mtDNA. Review Summary Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder of intergenomic communication and is defined clinically by 1) severe gastrointestinal dysmotility; 2) cachexia; 3) ptosis, ophthalmoparesis, or both; 4) peripheral neuropathy; and 5) leukoencephalopathy. Skeletal muscle biopsies of patients have revealed abnormalities of mtDNA and mitochondrial respiratory chain enzymes. The disease is caused by mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of thymidine to thymine and deoxyribose 1-phosphate. In MNGIE patients, TP enzyme activity is reduced drastically, and plasma thymidine and deoxyuridine are elevated dramatically. We have hypothesized that alterations of nucleoside metabolism cause an imbalanced mitochondrial nucleotide pool that leads to depletion and deletions of mtDNA. Conclusions MNGIE is a recognizable clinical syndrome caused by mutations in TP. The diagnosis can be confirmed by measuring TP activity in buffy coat or plasma levels of thymidine and deoxyuridine. Reduction of circulating thymidine and deoxyuridine in MNGIE patients may be therapeutic.
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