目的:没有眼外肌受累的线粒体肌病(MiMy)代表了一种独特的线粒体疾病,主要影响近端/远端或轴向肌。它的表型,基因型特征,和长期预后知之甚少。
方法:在国家线粒体疾病诊断中心进行的一项横断面研究涉及47名MiMy患者,从2000年1月1日至2021年1月1日在齐鲁医院随访的643例线粒体疾病病例队列中。我们比较了临床,病态,以及MiMy对进行性眼外肌麻痹(PEO)和线粒体脑肌病的遗传特征,乳酸性酸中毒,和中风样发作(MELAS)患者。
结果:MiMy患者表现出更明显的肌肉受累综合征,6MWT分数较低,更高的FSS,与PEO和MELAS患者相比,BMI较低。血清肌酐激酶(CK)水平,乳酸,MiMy患者的生长和分化因子15(GDF15)显著升高。近三分之一(31.9%)显示亚临床周围神经病变的迹象,主要是轴索神经病。肌肉活检显示,细胞色素c氧化酶强(COX-s)参差不齐的红色纤维(RRF)是MiMy患者的典型病理特征。遗传分析主要显示mtDNA点致病变异(59.6%)和较少频率的单个(12.8%)或多个(4.2%)mtDNA缺失。在后续行动中,大多数(76.1%)的MiMy患者在治疗干预后经历了稳定或改善.
结论:这项研究通过大型患者队列提供了MiMy的全面概况,阐明其独特的临床,遗传,和病理特征。这些发现为MiMy的诊断和治疗管理提供了重要的见解,最终旨在改善患者预后并提高生活质量。
OBJECTIVE: Mitochondrial myopathy without extraocular muscles involvement (MiMy) represents a distinct form of mitochondrial disorder predominantly affecting proximal/distal or axial muscles, with its phenotypic, genotypic features, and long-term prognosis poorly understood.
METHODS: A cross-sectional study conducted at a national diagnostic center for mitochondrial disease involved 47 MiMy patients, from a cohort of 643 mitochondrial disease cases followed up at Qilu Hospital from January 1, 2000, to January 1, 2021. We compared the clinical, pathological, and genetic features of MiMy to progressive external ophthalmoplegia (PEO) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients.
RESULTS: MiMy patients demonstrated a more pronounced muscle involvement syndrome, with lower 6MWT scores, higher FSS, and lower BMI compared to PEO and MELAS patients. Serum levels of creatinine kinase (CK), lactate, and growth and differentiation factor 15 (GDF15) were substantially elevated in MiMy patients. Nearly a third (31.9%) displayed signs of subclinical peripheral neuropathy, mostly axonal neuropathy. Muscle biopsies revealed that cytochrome c oxidase strong (COX-s) ragged-red fibers (RRFs) were a typical pathological feature in MiMy patients. Genetic analysis predominantly revealed mtDNA point pathogenic variants (59.6%) and less frequently single (12.8%) or multiple (4.2%) mtDNA deletions. During the follow-up, a majority (76.1%) of MiMy patients experienced stabilization or improvement after therapeutic intervention.
CONCLUSIONS: This study provides a comprehensive profile of MiMy through a large patient cohort, elucidating its unique clinical, genetic, and pathological features. These findings offer significant insights into the diagnostic and therapeutic management of MiMy, ultimately aiming to ameliorate patient outcomes and enhance the quality of life.