一例线粒体呼吸链复合物Ⅰ缺陷所致Leigh综合征:临床特点、治疗分析及基因突变研究  

A case of Leigh syndrome caused by mitochondrial respiratory chain complexes Ⅰ defects:clinical characteristics,treatment,and mutation analysis

作　　者：刘舒[1] 陈暖[1] 梁金群[1] 欧阳海梅[1] 曾伟宏[1] 谢汛杰 陈丽莹[1] 江剑辉[1] 

机构地区：[1]广东省妇幼保健院儿童遗传代谢与内分泌科,广州番禺511442

出　　处：《中国优生与遗传杂志》2017年第7期30-32,29,共4页Chinese Journal of Birth Health & Heredity

摘　　要：目的 Leigh综合征是由于线粒体呼吸链能量代谢障碍所导致的遗传性疾病,是婴幼儿时期最常见的线粒体脑病之一,其发病的主要机制是由于线粒体呼吸链氧化磷酸化障碍,ATP合成减少,乳酸堆积,导致严重神经肌肉损伤,进而出现一系列的临床症状。目前国内外研究证实,线粒体呼吸链5种酶复合物(Ⅰ、Ⅱ、Ⅲ、Ⅳ和Ⅴ)缺陷、丙酮酸脱氢酶复合物缺陷以及线粒体转运RNA突变等均可引起Leigh综合征。由于线粒体病最常累及能量需求大的器官,如脑、心脏、肝、骨骼肌、肾等,导致多脏器损害,因此患者临床表现复杂多样,从婴幼儿早期发病的致死性脑病到成年期起病的神经退行性疾病,有许多交叉重叠现象,仅借助于临床表现很难确诊,常需借助线粒体呼吸链酶活性测定、基因检测等方法。方法本研究中,患儿为第一胎,1岁时出现体格、智力发育落后,伴跛行和言语不清,呈进行性加重。血液乳酸增高,脑MRI显示双侧基底节对称性损害,符合Leigh综合征诊断。结果我们通过新一代测序技术进行线粒体全基因突变分析,证实患儿存在线粒体ND3基因10191T>C突变,导致线粒体呼吸链酶复合物I活性下降。患儿治疗以多种维生素为主,补充左旋肉碱、辅酶Q10,同时辅以生酮饮食治疗。治疗半年后,患者智力无明显倒退,但肌力、体重显著减退。结论我们通过高通量捕获测序技术,首次诊断了编码线粒体呼吸链复合物Ⅰ亚基的ND3基因10191T>C突变导致复合物Ⅰ缺陷,为疾病的确诊提供了依据,更为后期的精确治疗打下坚实的基础。Objective： Leigh syndrome is a kind of inherited metabolic disease common in infancy, which is caused by mitochondrial oxidative phosphorylation defects, reduced ATP synthesis, lactic acid accumulation. Studies of domestic and aboard have shown that 5 kinds of mitochondrial respiratory chain enzyme complexes （ I , II, III, IV and V ） defects, pyruvate dehydrogenase complex defects and mutations of mitochondrial tRNA can cause Leigh syndrome. Since mitochondrial disease most commonly affects the organs which have more energy consumption, such as brain, heart, liver, skeletal muscle, kidney and so on, leading to complex and diverse clinical manifestations of the patients. So, Leigh syndrome is difficult to be diagnosed by clinical manifestation, often need a mitochondrial respiratory chain enzyme activity testing, genetic testing, etc. Methods： In our study, the clinical manifestations of the child are consistent with Leigh syndrome, and we confirmed the diagnosis by a new generation of sequencing technology on mitochondrial gene （ND3 gene, 10191 T 〉C） , and the mutation of the ND3 gene led to a decline of enzymatic activity of mitochondrial respiratory chain enzyme complex I. activity. Resuts： The treatment of the patient are mainly with a variety of vitamins, L-carnitine, coenzyme Q10, and ketogenic diet therapy. After six months＇ treatment, the patients with no obvious mental regression, but the muscle strength and weight decreased significantly. Conclusion： We diagnosed a child with Leigh syndrome leading by decline of enzymatic activity of mitochondrial respiratory chain enzyme complex I for the first time, through high-throughput sequencing technology, which provided evidence for diagnosis of the disease, and laid a solid foundation for further accurate therapy.

关 键 词：LEIGH综合征 线粒体呼吸链复合物Ⅰ缺陷 ND3基因 突变 

分 类 号：R440[医药卫生—诊断学] R725.9[医药卫生—临床医学]