PDF(Pubmed)
Abstract：
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease caused by mutations in TYMP, the gene encoding for the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a systemic accumulation of thymidine and 2\'-deoxyuridine and ultimately mitochondrial failure due to a progressive acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. MNGIE is characterised by gastrointestinal dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, ptosis and leukoencephalopathy. The disease is progressively degenerative and leads to death at an average age of 37.6 years. Patients invariably encounter misdiagnoses, diagnostic delays, and non-specific clinical management. Despite its rarity, MNGIE has invoked much interest in the development of therapeutic strategies, mainly because it is one of the few mitochondrial disorders where the molecular abnormality is metabolically and physically accessible to manipulation. This review provides a resume of the current diagnosis and treatment approaches and aims to increase the clinical awareness of MNGIE and thereby facilitate early diagnosis and timely access to treatments, before the development of untreatable and irreversible organ damage.
摘要：
线粒体神经胃肠脑肌病（MNGIE）是一种由TYMP突变引起的超罕见疾病，编码酶胸苷磷酸化酶的基因。所产生的酶缺乏导致胸苷和2'-脱氧尿苷的系统性积累，并最终导致线粒体衰竭，这是由于逐渐获得继发性线粒体DNA（mtDNA）突变和mtDNA耗竭。MNGIE的特征是胃肠动力障碍，恶病质,周围神经病变,眼肌麻痹,眼睑下垂和白质脑病。该疾病逐渐退化并导致死亡，平均年龄为37.6岁。患者总是会被误诊，诊断延迟，和非特异性临床管理。尽管它很罕见,MNGIE引起了人们对发展治疗策略的极大兴趣，主要是因为它是少数线粒体疾病之一，其中分子异常是代谢和物理上可操作的。这篇综述提供了当前诊断和治疗方法的简历，旨在提高MNGIE的临床认识，从而促进早期诊断和及时获得治疗。在无法治愈和不可逆转的器官损伤发展之前。
