Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment.
Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment.
复制标题
DOI：
10.20517/jtgg.2020.08
复制
发表时间：
2020-03-30
期刊：
影响因子：
--
通讯作者：
Bax, Bridget E
中科院分区：
文献类型：
--
作者：
Bax, Bridget E
线粒体神经胃肠脑肌病（MNGIE）是一种由编码胸苷磷酸化酶的基因TYMP突变引起的极其罕见的疾病。由此产生的酶缺乏导致胸苷和2 '-脱氧尿苷的全身积累，并最终由于次级线粒体DNA（mtDNA）突变和mtDNA耗尽的进行性获得而导致线粒体衰竭。MNGIE的特征在于胃肠动力障碍、恶病质、周围神经病、眼肌麻痹、上睑下垂和白质脑病。这种疾病是逐渐退化的，导致死亡的平均年龄为37.6岁。病人总是会遇到误诊，诊断延误，和非特异性的临床管理。尽管其罕见，但MNGIE在治疗策略的开发中引起了很大的兴趣，主要是因为它是少数几种线粒体疾病之一，其中分子异常在代谢和物理上可被操纵。本文综述了目前的诊断和治疗方法，旨在提高MNGIE的临床意识，从而促进早期诊断和及时获得治疗，在发展不可治疗和不可逆的器官损伤之前。
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.