Nishino I, Spinazzola A, Papadimitriou A, Hammans S, Steiner I, Hahn C D, Connolly A M, Verloes A, Guimarães J, Maillard I, Hamano H, Donati M A, Semrad C E, Russell J A, Andreu A L, Hadjigeorgiou G M, Vu T H, Tadesse S, Nygaard T G, Nonaka I, Hirano I, Bonilla E, Rowland L P, DiMauro S, Hirano M
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Ann Neurol. 2000 Jun;47(6):792-800.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder defined clinically by severe gastrointestinal dysmotility; cachexia; ptosis, ophthalmoparesis, or both; peripheral neuropathy; leukoencephalopathy; and mitochondrial abnormalities. The disease is caused by mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of thymidine to thymine and deoxyribose 1-phosphate. We identified 21 probands (35 patients) who fulfilled our clinical criteria for MNGIE. MNGIE has clinically homogeneous features but varies in age at onset and rate of progression. Gastrointestinal dysmotility is the most prominent manifestation, with recurrent diarrhea, borborygmi, and intestinal pseudo-obstruction. Patients usually die in early adulthood (mean, 37.6 years; range, 26-58 years). Cerebral leukodystrophy is characteristic. Mitochondrial DNA (mtDNA) has depletion, multiple deletions, or both. We have identified 16 TP mutations. Homozygous or compound heterozygous mutations were present in all patients tested. Leukocyte TP activity was reduced drastically in all patients tested, 0.009 +/- 0.021 micromol/hr/mg (mean +/- SD; n = 16), compared with controls, 0.67 +/- 0.21 micromol/hr/mg (n = 19). MNGIE is a recognizable clinical syndrome caused by mutations in thymidine phosphorylase. Severe reduction of TP activity in leukocytes is diagnostic. Altered mitochondrial nucleoside and nucleotide pools may impair mtDNA replication, repair, or both.
线粒体神经胃肠性脑肌病（MNGIE）是一种常染色体隐性疾病，临床特征为严重的胃肠动力障碍、恶病质、上睑下垂、眼肌麻痹或两者皆有、周围神经病变、白质脑病以及线粒体异常。该疾病由胸苷磷酸化酶（TP）基因突变引起。TP蛋白催化胸苷磷酸解为胸腺嘧啶和脱氧核糖1-磷酸。我们确定了21名符合我们MNGIE临床标准的先证者（35名患者）。MNGIE具有临床同质性特征，但发病年龄和进展速度有所不同。胃肠动力障碍是最突出的表现，伴有反复腹泻、肠鸣音和肠道假性梗阻。患者通常在成年早期死亡（平均37.6岁；范围26 - 58岁）。脑白质营养不良是其特征。线粒体DNA（mtDNA）存在耗竭、多处缺失或两者皆有。我们已确定16种TP突变。所有检测患者均存在纯合或复合杂合突变。与对照组[0.67±0.21微摩尔/小时/毫克（n = 19）]相比，所有检测患者的白细胞TP活性均大幅降低，为0.009±0.021微摩尔/小时/毫克（平均±标准差；n = 16）。MNGIE是一种由胸苷磷酸化酶突变引起的可识别临床综合征。白细胞中TP活性严重降低具有诊断意义。线粒体核苷和核苷酸池的改变可能损害mtDNA复制、修复或两者皆有。
