POLG突变引起的线粒体神经胃肠型脑肌病样综合征的临床特征

目的 探讨线粒体聚合酶γ基因(Polymerase gamma, POLG)突变引起的线粒体神经胃肠型脑肌病(Mitochondrial neurogastrointestinal encephalomyopathy, MNGIE)样综合征患者的临床特征。方法 报道1例POLG突变引起的MNGIE样综合征患者的临床资料,并检索建库至2022年9月的中国知网、万方中文数据库和PubMed数据库中关于POLG突变引起的MNGIE样综合征的病例,从而总结该疾病的临床特点。结果 本例患者为6月龄女婴,以胃肠道症状及运动发育落后为主要表现,脑脊液蛋白水平升高,肌电图示周围神经损害,高通量测序分析发现POLG基因2个杂合突变点,分别为c.2591A>G和c.2962G>C。回顾文献,本研究共纳入11例(含本例)POLG突变引起的MNGIE样综合征患者;起病年龄为3月龄-42岁,临床症状包括胃肠道症状(11例)、周围神经损害(11例)、上睑下垂(9例)、肌无力或运动不耐受(9例)、运动发育落后(2例)、共济失调(4例)、视力障碍(3例)、听力障碍(2例)、认知障碍或智力低下(2例)、癫痫...     

TYMP基因新突变型线粒体神经胃肠脑肌病1例报告及文献回顾

目的探讨线粒体神经胃肠脑肌病患者的临床表现及基因突变情况。方法分析1例线粒体神经胃肠脑肌病患者的临床资料。提取外周血单核细胞DNA进行基因测序。结果该患者表现为进行性加重的胃肠道症状、脑白质病、恶液质、周围神经病及眼外肌无力。基因检测发现TYMP基因c.417+1GA纯合变异为该患者的致病突变,该突变为新发突变。结论经基因检测确诊TYMP基因新发突变致线粒体神经胃肠脑肌病。     

TYMP基因新杂合突变致早发型线粒体神经胃肠型脑肌病1例报告并文献复习

线粒体神经胃肠型脑肌病(mitochondrial neurogastroint-estinal encephalomyopathy,MNGIE)是一种罕见的常染色体隐性遗传的多系统疾病,由于核基因TYMP突变导致胸苷磷酸化酶(thymidine phosphorylase,TP)缺陷所致[1].TP的活性降低或缺失,...     

线粒体脑肌病

线粒体脑肌病郭玉璞一、概述线粒体是人体最重要的产生能量的细胞器，是人体细胞主要能量来源，其基本功能是氧化可利用的底物，通过呼吸链电子传递合成ＡＴＰ。它含有全套呼吸链酶体系、氧化磷酸化酶体系三羧酸循环、脂肪酸氧化酶等，线粒体ＤＮＡ（ｍｔＤＮＡ）是人体细...     

线粒体神经胃肠型脑肌病

线粒体神经胃肠型脑肌病(Mitochondrial Neurogastroint-estinal Encephalopathy Disease,MNGIE)是一种特殊类型的线粒体肌病,又被称为多发性神经病伴眼肌麻痹、白质脑病、假性肠梗阻(polyneuropathy ophthalmoplegia leukoencephalop-athy and intestinal pseudo-obstruction,POLIP),眼部及胃肠     

线粒体脑肌病

线粒体脑肌病王纪佐姚小梅近年来，遗传学的发展更新了人们对疾病的认识。其中进展最快的当属线粒体遗传学中由于线粒体ＤＮＡ（ｍｔＤＮＡ）突变所造成的疾病研究。线粒体病在６０年代初始见报道，１９６６年Ｓｈｙ等确定了一类儿童肌病，电子显微镜发现其增大的线粒体中...     

线粒体脑肌病的临床与病理

目的探讨线粒体脑肌病的临床与肌肉病理特点。方法对16例肌活检证实的线粒体脑肌病病例的临床表现、肌肉组织化学及超微结构进行分析。结果16例患者破碎红纤维(RRF)的平均比例为5.9%,11例有中央核增多,13例的SDH/CCO双染示12例有蓝纤维,且与RRF的分布一致。超微结构观察有4例找到典型晶格状包涵体。结论SDH/CCO双染有蓝纤维为线粒体肌病的诊断提供了依据,借此可与其他肌病鉴别。     

线粒体肌病和脑肌病现状

线粒体肌病和脑肌病现状刘永刚（综述）熊先骥（校）线粒体是存在于每个细胞内的除了细胞核以外唯一含有独立的ＤＮＡ复制系统的细胞器，其主要功能是合成三磷酸腺苷，为细胞代谢提供充足的能量。线粒体肌病是一组由于线粒体结构和功能异常所致的疾病，病变以侵犯骨骼肌为...     

MELAS型线粒体脑肌病1例临床病理

目的分析1例MELAS型线粒体脑肌病的临床病理特点。方法对该患者的临床、实验室、影像学及肌肉病理特点进行回顾性分析。结果血和脑脊液乳酸高,头颅CT、MRI显示病灶局限于颞顶枕部,肌肉活检证实患者的骨骼肌存在大量典型的不整边红纤维。结论对年轻患者反复表现为卒中样发作、局限性或全面性癫痫,病灶局限于颞顶枕部,应行肌肉活检,避免误诊。     

A novel TYMP mutation in a French Canadian patient with mitochondrial neurogastrointestinal encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder characterized by gastrointestinal, extraocular muscle, peripheral nerve, and cerebral white matter involvement. Mutations in the nuclear gene TYMP encoding for thymidine phosphorylase (TP) cause loss of TP activity, systemic accumulation of its substrates in plasma and tissues, as well as alterations in mitochondrial DNA including deletions, depletion, and somatic point mutations. To date, more than 30 mutations have been reported in diverse ethnic populations. We present herein the clinical, neuroimaging, neuromuscular, and molecular findings of the first French Canadian patient with MNGIE caused by a novel homozygous invariant splicing site (IVS5 +1 G>A) mutation of the TYMP gene.     

Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the thymidine phosphorylase gene ( ECGF1 ). We present the first detailed report of a Brazilian MNGIE patient, harboring a novel ECGF1 homozygous mutation (C4202A, leading to a premature stop codon, S471X). Multiple deletions and the T5814C change were found in mitochondrial DNA. Together with gastrointestinal symptoms, endocrine involvement and memory dysfunction, not reported in MNGIE to date, were the most preeminent features.     

MELAS综合征的临床、病理和动态影像学表现

目的 探讨线粒体脑肌病伴乳酸血症和脑卒中发作(MELAS综合征)的临床、病理和动态影像学表现特点. 方法 回顾性分析经肌肉活检病理证实的10例MELAS综合征患者的临床、病理及动态影像学资料. 结果 MELAS综合征患者的主要临床表现为头痛、癫痫、恶心呕吐、眼球震颤、视力障碍.CT显示病变较差,MR能清晰显示病变,病变多位于颞叶、顶叶、枕叶皮层及皮层下,呈脑回状,具有多灶性、非对称性、游走性、不按血管分布特点,MRA多无明显血管狭窄,病变区呈现高灌注和血管源性水肿,MRS可见乳酸(Lac)峰.肌肉病理活检光镜下显示破碎红纤维、强阳性血管,电镜下见线粒体数量增多、大小和形态异常. 结论 MELAS综合征的临床和影像学表现具有一定特点,结合肌肉病理活检可对该病进行早期诊断和鉴别诊断.     

The Alzheimer's disease mitochondrial cascade hypothesis: An update

In 2004 we proposed the mitochondrial cascade hypothesis of sporadic Alzheimer's disease (AD). Our hypothesis assumed sporadic and autosomal dominant AD are not etiologically homogeneous, considered evidence that AD pathology is not brain-limited, and incorporated aging theory. The mitochondrial cascade hypothesis asserted: (1) inheritance determines mitochondrial baseline function and durability; (2) mitochondrial durability influences how mitochondria change with age; and (3) when mitochondrial change reaches a threshold, AD histopathology and symptoms ensue. We now review the reasoning used to formulate the hypothesis, discuss pertinent interim data, and update its tenants. Readers are invited to consider the conceptual strengths and weaknesses of this hypothesis.     

Absence of the interstitial cell of Cajal network in mitochondrial neurogastrointestinal encephalomyopathy

Abstract  Mitochondrial neurogastrointestinal enceph-alomyopathy (MNGIE) is a rare autosomal-recessive multisystemic disorder with predominant gastrointestinal involvement, presenting with variable degrees of gut dysmotility up to frank chronic intestinal pseudoobstruction. Despite major advances in understanding its basic molecular pathogenesis in recent years, the distinct mechanisms and pathoanatomical substrate underlying MNGIE-associated gastrointestinal dysmotility are still widely unknown. As yet, though their critical role in proper gastrointestinal transit in terms of spontaneous pacemaker activity and enteric neurotransmission is well established, the population of the interstitial cells of Cajal (ICC) has not been investigated in MNGIE. Therefore, we examined small bowel samples of a well-characterized MNGIE patient by using conventional histology and immunohistochemistry techniques. The ICC network was studied by immunohistochemistry for the tyrosine kinase Kit (CD117), known to reliably detect ICCs, while mucosal mast cells served as an internal and normal small bowel specimen as external controls. At a light microscopic level, no gross structural alteration of the bowel wall composition and its neuromuscular elements was noted. However, a complete absence of Kit immunoreactive cells could be demonstrated in regions where ICCs are normally abundant, while internal and external controls retained strong Kit positivity. In conclusion, our preliminary results provide a first evidence for an alteration of the ICC network in MNGIE, and support the notion that ICC loss might be an early pathogenetic event in MNGIE-associated gut motor dysfunction before significant myopathic and/or neuropathic structural changes occur.     

Wernicke脑病的临床、影像学及病理特点

目的探讨Wernicke脑病的临床、影像学及病理特点。方法回顾性分析10例Wernicke脑病患者的临床、影像学及病理资料。结果本组10例均非乙醇中毒患者,临床表现为不同程度的精神及意识障碍9例,首发症状为眩晕、恶心和呕吐6例,眼肌瘫痪5例,低血压3例,共济失调2例,严重的周围神经病变1例。5例行头颅MRI检查,3例表现为第三、四脑室及中脑导水管周围对称性的长T1长T2异常信号,2例无阳性发现。经补充维生素B1明显好转4例,死亡5例,放弃治疗1例。5例尸检脑部表现为第三、四脑室及中脑导水管周围灰质充血、水肿和点状出血。结论Wernicke脑病临床表现不典型,MRI检查可为Wernicke脑病的早期诊断提供帮助,及早补充维生素B1是治疗的关键。     

五例MELAS综合征的临床分析

目的 报道5例线粒体脑肌病伴乳酸酸中毒和卒中样发作(MELAS)综合征患者的临床、肌肉病理表现和近期随访结果. 方法 同顾性分析安徽中医学院神经病学研究所附属医院神经内科自2008年12月至2011年6月5例MELAS综合征患者的临床表现、血清酶学、电生理、影像学、肌肉活检组织病理及近期随访的结果. 结果 3例首发症状为头痛,以偏瘫和上消化道出血为首发症状各1例,病程中有全身抽搐发作4例,精神症状2例.肌酸激酶4例正常,1例轻度升高.肌电图4例未见异常,1例肌源性损害.头颅MRI示5例均有明显异常,以永久性脑梗死和脑萎缩为主.肌肉组织病理检查5例均发现强反应性血管(SSVs),且SSVs的细胞色素C氧化酶的酶活性增强.经过线粒体保护等综合治疗,随访6个月3例已恢复到能正常工作,2例病情轻度好转. 结论 MELAS综合征患者的头颅MRI均有明显异常,肌活检组织病理及组织酶学染色是诊断该病关键手段,一般预后良好.     

Creutzfeldt—Jakob病的临床及病理分析

目的 探讨Creutzfeldt-Jakob病（CJD）的临床特点及诊断,提高生前确诊率。方法 对4例经病理证实的CJD患者的临床表现、光镜及电镜所见进行分析。结果 4例均具有典型的临床表现,病理可见神经细胞变性死亡,胶质细胞增生,无炎性改变,电镜除可见上述改变外,还可见部分髓鞘及轴索的肿胀、变性。结论 此病多为散发性,无特殊有效治疗,预后差。临床病理检查是确诊CJD的最佳检查方法。     

线粒体胃肠肌病二例的临床与病理研究

目的 报道2例以胃肠道功能异常和肌无力为主要表现的线粒体病，探讨本病的诊断规律。方法 2例男性患者分别为13岁和6岁，在6岁和4岁5个月时起反复出现胃肠道症状和持续性肌无力，无眼外肌瘫痪和中枢神经系统损害的表现，头颅CT和MRI检查无异常，对2例患者进行肌肉活检和线粒体基因检查。结果 肌肉活检证实2例患者的骨骼肌存在大量典型的不整红边纤维和琥珀酸脱氢酶深染的肌纤维，肌纤维内糖原和脂肪滴增多。电镜检查显示肌纤维内出现大量巨大线粒体，部分线粒体内出现环状排列的嵴或类结晶包涵体，肌纤维内糖原和脂肪滴增多。基因检查示2例患者分别存在线粒体基因3243点突变和3271点突变。结论 胃肠道功能异常和肌无力可以作为主要临床症状组合出现在线粒体病中，由于2例患者的临床表现不同于以前报道的线粒体脑肌病，应诊断为线粒体胃肠肌病，可能属于线粒体病一个新的临床病理亚型。在寻找儿童慢性胃肠功能异常的病因时应考虑到本病的可能。