核黄素反应性脂质沉积性肌病临床特征与基因突变分析:两家系三例报告并文献复习  

Clinical characteristics and gene mutation analysis of riboflavin-responsive lipid storage myopathy: report of 3 cases in 2 families and review of literature

作　　者：操基清[1] 张成[1] 李亚勤[1] 杨娟[2] 梁颖茵[1] 冯善伟[1] 张旭[3] 利婧[1] 张惠丽[1] 朱瑜龄[1,4] 耿嘉[5] 杨丽卿[6] 

机构地区：[1]中山大学附属第一医院神经科,广州510080 [2]南方医科大学珠江医院神经内科,广州510282 [3]空军航空医学研究所附属医院分子病理中心,北京100089 [4]中山大学中山医学院解剖教研室,广州510080 [5]昆明医学院第一附属医院神经内科,650032 [6]山东省烟台毓璜顶医院神经内科,264000

出　　处：《中国现代神经疾病杂志》2014年第6期479-484,共6页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：国家自然科学基金-广东省联合基金重点资助项目(项目编号:U1032004);国家自然科学基金资助项目(项目编号:30870851);国家自然科学基金资助项目(项目编号:81271401);国家科技支撑计划项目(项目编号:2012BAI09B04);国家科技重大专项课题-重大新药创制(项目编号:2011ZX09307-001);广东省科技计划项目(项目编号:2011A030400006);广东省人口和计划生育委员会科技项目(项目编号:2009208);广东省人口和计划生育委员会重点项目(项目编号:2010102)~~

摘　　要：目的分析核黄素反应性脂质沉积性肌病临床特征和基因型,以实现早期诊断与治疗。方法与结果两家系3例核黄素反应性脂质沉积性肌病患者主要表现为进行性呼吸肌、四肢近端肌无力,肌电图呈肌源性损害,油红O染色肌纤维内可见脂肪滴沉积。3例患者均存在电子转移黄素蛋白脱氢酶(ETFDH)基因突变,分别为c.250G>A(Ala84Thr)纯合突变和c.250G>A(Ala84Thr)、c.524G>A(Arg175His)复合杂合突变。维生素B2治疗后症状明显改善,1例治疗10个月后呼吸肌和四肢近端肌无力症状完全消失,恢复正常运动功能;1例治疗2个月后行走、跑步如常,颈部肌肉恢复至正常状态;1例治疗2个月后可参加剧烈运动且无疲劳感。结论核黄素反应性脂质沉积性肌病虽然以四肢近端和躯干肌无力,以及运动不耐受为主要表现,但也需注意少数以呼吸肌无力为首发症状的病例,避免漏诊和误诊。维生素B2单药治疗效果极佳,症状可明显好转或痊愈。因此,临床疑似核黄素反应性脂质沉积性肌病患者可尝试维生素B2诊断性治疗。Objective The clinical manifestation and electron transfer flavoprotein dehydrogenase （ETFDH） gene mutation of riboflavin-responsive lipid storage myopathy were analyzed for early diagnosis and treatment. Methods Clinical material, ETFDH gene mutation and the motor function before and after vitamin B2 treatment in 3 patients from 2 predigrees were collected from August 2012 to March 2013 in our hospital. Results Case 1 was 16-year-old female. The chief complaint was difficulty of breathing and expectorating for over 3 years. Clinical symptoms included progressive respiratory muscle and proximal limb muscle weakness and worsen by fever, cardiac involvement, myopathic electromyography （EMG） changes and deposition of lipid droplets in muscle fiber by oil red O staining. Case 2 and Case 3 were brothers, the chief complaint of whom was fatigue after exercise for more than 1 year and 1 month, respectively. Clinical symptoms included significantly weakness of lower limbs and neck muscles after exercise and myopathic EMG changes. All 3 patients from two predigrees presented ETFDH gene mutation [c.250G 〉 A （Ala84Thr） homozygous mutations and c.250G 〉 A （Ala84Thr） and c.524G 〉 A （Arg175His） compound heterozygous mutations, respectively]. They all had a dramatic response to vitamin B2 treatment with muscle strength and motor function recovering to normal. The symptoms of Case 1 were completely disappeared with vitamin B2 treatment for over 10 months, including respiratory muscle and proximal limb muscle weakness, and the motor function of her limbs returned to normal, characterized by completing over 10 squat-stand in 1 rain. Case 2 could walk and run as ordinary people, raise his head without difficulty and play basketball about 2 h without fatigue after vitamin B2 treatment for over 2 months. Case 3 could participate in any kind of strenuous exercise without fatigue after vitamin B2 treatment for over 2 months. Conclusions Riboflavin-responsive lipid storage myopathy is mainly characterized by pr

关 键 词：脂质贮积病 电子转移黄素蛋白质类 基因 突变 

分 类 号：R746[医药卫生—神经病学与精神病学]