From St. George's (B.E.B., M.D.B.), University of London, UK; Institute of Neurology (M.S., P.T.), University of Verona; University Hospital "Spedali Civili" (M.F.), Brescia, Italy; and Kings College Hospital (N.M.), London, UK.
Neurology. 2013 Oct 1;81(14):1269-71. doi: 10.1212/WNL.0b013e3182a6cb4b. Epub 2013 Aug 21.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive metabolic disorder caused by a deficiency of thymidine phosphorylase (TP, EC2.4.2.4) due to mutations in the nuclear gene . TP deficiency leads to plasma and tissue accumulations of thymidine and deoxyuridine which generate imbalances within the mitochondrial nucleotide pools, ultimately leading to mitochondrial dysfunction. MNGIE is characterized clinically by leukoencephalopathy, external ophthalmoplegia, peripheral polyneuropathy, cachexia, and enteric neuromyopathy manifesting as gastrointestinal dysmotility. The condition is relentlessly progressive, with patients usually dying from a combination of nutritional and neuromuscular failure at an average age of 37 years. Allogeneic hematopoietic stem cell transplantation (AHSCT) offers a permanent cure. Clinical and biochemical improvements following AHSCT have been reported but it carries a high mortality risk and is limited by matched donor availability. A consensus proposal for standardizing AHSCT recommends treatment of patients without irreversible end-stage disease and with an optimally matched donor; a majority of patients are ineligible and thus there is a critical requirement for an alternative treatment.
线粒体神经胃肠型脑肌病（MNGIE）是一种罕见的常染色体隐性代谢疾病，由核基因中的胸苷磷酸化酶（TP，EC2.4.2.4）缺乏引起，由于基因突变导致血浆和组织中胸苷和脱氧尿苷的积累，从而导致线粒体核苷酸池失衡，最终导致线粒体功能障碍。MNGIE 临床上表现为脑白质病、眼外肌麻痹、周围性多发性神经病、恶病质和肠神经肌病，表现为胃肠道动力障碍。该疾病呈进行性加重，患者通常因营养和神经肌肉衰竭的综合作用而在平均 37 岁时死亡。异基因造血干细胞移植（AHSCT）提供了永久性治愈方法。报道称，AHSCT 后临床和生化改善，但它具有很高的死亡率，且受到匹配供体可用性的限制。一项关于 AHSCT 标准化的共识建议建议治疗没有不可逆终末期疾病且有最佳匹配供体的患者；大多数患者不符合条件，因此迫切需要替代治疗。
