摘要目的:总结携带MT-TK基因m.8344A>G变异患儿的临床特征。方法:病例系列研究，回顾性收集2012年1月至2024年1月于首都医科大学附属北京儿童医院神经内科就诊的22例MT-TK基因m.8344A>G变异临床诊断线粒体病患儿的病例资料，对患儿临床表现、实验室检查、肌肉病理、基因检测及肌阵挛治疗的随访结果进行分析。采用Pearson相关分析进行相关性分析。结果:22例MT-TK基因m.8344A>G变异患儿中男13例、女9例，起病年龄5.00（2.75，9.00）岁。15例为肌阵挛性癫痫伴破碎红纤维病（MERRF），3例Leigh综合征（LS），4例为LS和MERRF重叠综合征（LS-MERRF）。15例MERRF患儿均存在肌阵挛表现，其中10例为首发症状，5例在病程中出现且随病程呈进行性加重，主要以局灶性肌阵挛为主，多在精细动作或精神紧张时加重。15例MERRF中10例脑电图监测到肌阵挛发作（6例提示为肌阵挛癫痫发作，4例提示为皮层下肌阵挛）；2例合并全面性肌阵挛发作，合并失神发作和发全面性癫痫发作各1例；12例存在小脑共济失调；10例存在运动不耐受；8例存在肌无力；头颅磁共振成像检查1例脑室周围白质受累、1例双侧海马受累（癫痫频繁发作继发可能性大）。3例LS均存在发育倒退，其他伴随症状包括小脑共济失调、肌无力、吞咽困难等。4例LS-MERRF临床表现均叠加MERRF和LS的症状。7例LS和LS-MERRF的头颅磁共振成像显示，6例脑干受累（均累及中脑），4例基底节区受累。22例患儿血液标本中，m.8344A>G变异比例>90%共12例，>80%~90% 3例，>70%~80% 4例，>60%~70% 3例。血m.8344A>G变异比例与LS表型和起病年龄均相关（ r=0.47、-0.50， P=0.018、0.029）。19例患儿母亲完成血液样本m.8344A>G的Sanger测序，18例存在变异，其中4例存在运动不耐受症状。13例患儿对应用抗肌阵挛的药物治疗进行了随访，2例左乙拉西坦单药治疗肌阵挛发作减少75%以上，5例2种药联用，6例联合3种药物，13例均在肌阵挛出现的2年内药物控制有效，发作次数减少50%以上，但随病情进展各种抗癫痫药物疗效较差。 结论:m.8344A>G变异罕见，临床以MERRF最常见，LS及LS-MERRF较少见。血液中m.8344A>G变异比例较高的患儿更易出现LS表型，肌阵挛和肌病是其所致MERRF表型的重要特征。肌阵挛表现形式多变，局灶性为主，成因复杂，其控制首选左乙拉西坦，控制不佳时，应尽早加用苯二氮?类药物。

abstractsObjective:To summarize the clinical characteristics of children carrying the m.8344A>G variant of MT-TK gene.Methods:A case series study was conducted to retrospectively collect data of 22 children with mitochondrial disease caused by MT-TK gene m.8344A>G variation who were treated at the Department of Neurology of Beijing Children′s Hospital of Capital Medical University from January 2012 to January 2024. Their clinical data, laboratory tests, muscle pathology, genetic testing, and the follow-up results were analyzed. Pearson correlation analysis was used for correlation analysis.Results:Among the 22 children, there were 13 boys and 9 girls. The age of onset was 5.00 (2.75, 9.00) years. Fifteen children had myoclonic epilepsy with ragged-red fibers (MERRF), 3 had Leigh syndrome (LS), and 4 had LS-MERRF overlap syndrome (LS-MERRF). Myoclonus presented and worsened progressively in all 15 MERRF children, with 10 as the initial symptom and 5 developing progressively during the disease course. Myoclonus was predominantly focal, worsening with fine motor tasks or stress. Electroencephalogram monitoring in the 15 MERRF children revealed myoclonic seizures in 10 children, with 6 classified as myoclonic epilepsy, and 4 as subcortical myoclonus. Two children had generalized myoclonic seizures, and 1 each had absence seizures and generalized seizures. Twelve children had cerebellar ataxia, 10 children exhibited exercise intolerance, and 8 children had muscle weakness. Magnetic resonance imaging (MRI) revealed periventricular white matter involvement in 1 child and bilateral hippocampal involvement in 1 child, likely due to frequent seizures. All 3 children with LS exhibited developmental regressions, accompanied with 2 symptoms include cerebellar ataxia, muscle weakness, and dysphagia. The clinical manifestations of 4 LS-MERRF overlap children presented with combined features of MERRF and LS. Cranial MRI in the 7 LS and LS-MERRF children showed brainstem involvement (all affecting the midbrain) in 6 children and basal ganglia involvement in 4 children. Among the 22 children, 12 had m.8344A>G variant levels >90%, 3 had >80%-90%, 4 had >70%-80%, and 3 had >60%-70%. Higher variant level correlated with the LS phenotype and earlier onset age ( r=0.47, -0.50; P=0.018 and 0.029, respectively). Sanger sequencing in 19 mothers revealed m.8344A>G variations in 18, with 4 showing exercise intolerance. Follow-up of 13 children on antimyoclonic treatment showed>75% reduction in seizures with levetiracetam monotherapy in 2 children, with combination therapy required in others. Most achieved >50% seizures reduction within 2 years, but the effectiveness declined with disease progression. Conclusions:The m.8344A>G variant is rare, with MERRF being the most common phenotype, while LS and LS-MERRF are less common. Children with higher ratio of the m.8344A>G variant are more likely to present LS phenotype. Myoclonus, primarily focal, is a key feature, with levetiracetam as the first-line treatment and benzodiazepines recommended for refractory cases.