Objective: To investigate the ultrastructural features of muscle in patients with mitochondrial encephalomyopathy for its diagnosis and differential diagnosis. Methods: The clinical data of 27 mitochondrial encephalomyopathy patients who underwent left or right biceps brachii muscle biopsy at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from July 2006 to August 2017 were analyzed retrospectively. The muscle biopsy specimens were examined underlight microscope and transmission electron microscope. Results: There were 27 patients (17 males, 10 females) with an age range of 12 to 62 years (mean 29 years). The age of onset ranged from 3 to 38 years. The course of disease ranged from 1 month to 24 years. Twenty-two cases presented with lactic acidosis and stroke-like episodes (MELAS) syndrome, four with myoclonic epilepsy with ragged red fibers (MERRF) syndrome, and one with chronic progressive paralysis of extraocular muscle (CPEO) syndrome. Skeletal muscle biopsy showed abundant ragged red fibers and strongly SDH-reactive vessel. Genetic studies showed 17 of 22 cases of MELAS syndrome had A3243G mutation, and the other 5 cases had no abnormality. A8344G mutation was found in 3 of 4 cases of MERRF syndrome. No single or multiple mtDNA mutations were found in the single case of CPEO. Transmission electron microscopy of all 27 cases showed diffuse proliferation of mitochondria between the myofibrils and beneath the sarcolemma, with increased spacing between muscle cells. Seven cases showed numerous glycogen and four showed subsarcolemmal lipid droplets, 13 cases showed unusual mitochondrial morphology, including mitochondrial electron-dense substances and paracrystal line inclusions ("parking lot" change)in eight cases. Conclusions: Transmission electron microscopy shows significant differences in ultrastructural pathological changes among different patients with mitochondrial encephalomyopathy. Some patients with mild clinical symptoms have increased mitochondrial number, increased metabolism of glycogen and lipid droplets, while others with severe clinical symptoms have abnormal mitochondrial morphology. Typical crystalloid inclusions are found in mitochondria, which are of great value in the diagnosis of this disease.
目的： 探讨线粒体脑肌病患者肌肉的超微结构特征，分析其诊断和鉴别诊断，以提高临床对该病的认识。 方法： 收集首都医科大学附属北京天坛医院2006年7月至2017年8月间诊断的线粒体脑肌病27例，均经左侧或右侧肱二头肌肌肉活检。对27例线粒体脑肌病患者的临床资料进行回顾性分析，并且观察该组患者肌肉活检组织的光镜和电镜超微病理特征。 结果： 27例患者，男性17例，女性10例，年龄范围12~62岁，平均29岁，发病年龄3~38岁。病程1个月至24年。22例线粒体脑肌病伴高乳酸血症及卒中样发作（MELAS）综合征，4例肌阵挛性癫痫伴破碎红纤维（MERRF）综合征，1例慢性进行性眼外肌麻痹（CPEO）综合征。骨骼肌组织常规HE和酶组织化学Gomori三色、琥珀酸脱氢酶（SDH）染色均可见破碎红纤维，SDH染色可见肌间强血管反应。基因检测结果显示22例MELAS综合征中17例存在A3243G突变，其余5例未见异常。4例MERRF综合征中3例有A8344G突变。1例CPEO综合征未见mtDNA单个或多个基因突变。透射电镜下观察均出现横纹肌组织肌膜下或肌原纤维间线粒体数量增多，其中7例在肌丝缺失处伴有糖原颗粒增多，4例肌膜下伴有大量脂滴存在，13例线粒体形态怪异，其中8例可见典型结晶样包涵体，呈"停车坪样"改变，另外3例仅线粒体数量增多，未见其他异常。 结论： 不同的线粒体脑肌病患者，超微病理学改变存在显著差异。其中一部分临床症状相对较轻患者会出现线粒体数量增多，糖原和脂滴代谢增加，另外一部分临床症状相对较重的患者则出现线粒体形态异常，其中线粒体内出现典型类结晶样包涵体，对该病的诊断具有重要价值。.
Keywords: Intranuclear inclusion bodies; Microscopy, electron; Mitochondrial encephalomyopathies.