以肌无力为首发症状的脂质沉积性肌病:临床病理特征复发预测及ETFDH新突变OA
Lipid storage myopathy presenting with isolated muscle weakness as the initial symptom:Clinicopathological features,predictors of relapse,and a novel ETFDH mutation
目的 阐明以肌无力为首发症状的脂质沉积性肌病(LSM)患者的临床病理特征,评估血清肌酸激酶(CK)的动态监测价值,识别疾病复发的独立预测因素,并扩展其遗传学图谱.方法 回顾性分析38例经肌肉活检确诊、表现为孤立性肌无力的LSM患者.收集患者临床表型、CK、肌电图(EMG)及病理数据,采用靶向二代测序检测ETFA/B/DH基因.使用Cox比例风险模型分析停药后复发的预测因子.结果 患者平均发病年龄31.6岁,误诊率34.21%,常被误诊为多发性肌炎.肌肉活检除典型的脂滴积聚外,15.79%的患者出现肌纤维坏死,且与肌源性EMG改变显著相关.治疗前CK水平与髂腰肌肌力呈显著负相关(ρ=-0.72,P<0.001).随访期间复发率46.9%.多变量分析显示,治疗前CK水平>5 000 IU/L和存在坏死肌纤维是疾病复发的独立预测因素.遗传学分析在90%的受检者中检出ETFDH突变,并鉴定出一个位于泛醌结合结构域的新型错义突变c.1562C>T(p.Ser521Phe).结论 以肌无力为主的LSM患者具有独特的临床病理谱,极易误诊.除作为肌肉损伤标志物外,极高水平的CK结合组织学坏死特征提示严重的脂毒性损伤及较高的复发风险.研究提出的预测指标及新发现的突变位点,为该亚型患者的精准诊断和长期管理提供了重要依据.
Objective To elucidate the clinicopathological features of patients with lipid storage myopathy(LSM)presenting with isolated muscle weakness as the initial symptom,assess the dynamic value of serum creatine kinase(CK),identify independent predictors of disease recurrence,and expand its genetic profile.Methods A retrospective analysis was conducted on 38 LSM patients confirmed by muscle biopsy and presenting with isolated muscle weakness.Clinical phenotypes,CK levels,electromyography(EMG),and pathological data were collected.Targeted next-generation sequencing was performed for ETFA,ETFB,and ETFDH genes.Cox proportional hazards modeling was used to identified predictors of post-treatment relapse.Results The mean age of onset was 31.6 years,with a misdiagnosis rate of 34.21%(commonly as polymyositis).Muscle biopsy revealed lipid droplet accumulation in all cases,while 15.79%exhibited necrotic muscle fibers,significantly associated with myopathic EMG changes.Pre-treatment CK levels correlated negatively with iliopsoas muscle strength(ρ=-0.72,P<0.001).The relapse rate during follow-up was 46.9%.Multivariate analysis identified pre-treatment CK>5 000 IU/L(HR=2.3,95%CI:1.1-4.8,P=0.03)and necrotic fibers(HR=3.1,95%CI:1.4-6.9,P=0.006)as independent predictors of relapse.Genetic analysis detected ETFDH mutations in 90%of tested patients,including a novel missense mutation(c.1562C>T,p.Ser521Phe)in the ubiquinone-binding domain.Conclusion LSM patients with predominant muscle weakness exhibit unique clinicopathological features and high misdiagnosis rates.Extremely elevated CK and histological necrosis signify severe lipotoxic injury and predict relapse risk.The proposed predictors and novel mutation provide critical insights for precise diagnosis and long-term management.
张文;丁卫江;李学明
南昌大学第二附属医院,江西 南昌 330000南昌大学第二附属医院,江西 南昌 330000南昌大学第二附属医院,江西 南昌 330000
医药卫生
脂质沉积性肌病多酰基辅酶A脱氢酶缺乏症ETFDH基因肌酸激酶肌纤维坏死复发
Lipid storage myopathyMultiple acyl-CoA dehydrogenase deficiencyETFDH geneCreatine kinaseMuscle fiber necrosisRelapse
《中国实用神经疾病杂志》 2026 (10)
1194-1200,7
江西省卫健委科技计划项目(编号:202610452)江西中医药管理局科技计划项目(编号:2025020026)
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