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。

关键词: 脂质贮积病, 电子转移黄素蛋白质类, 基因, 突变

Abstract: 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.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 min. 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 proximal limb and trunk muscle weakness and intolerance of movement, however, rare cases with first symptom of respiratory muscle weakness should also be concerned. In addition, it is a treatable genetic disease. The patients could be cured or significantly improved with vitamin B₂ monotherapy. So vitamin B₂ exploratory treatment should be given when the patients are suspected of riboflavin-responsive lipid storage myopathy.

Key words: Lipidoses, Electron-transferring flavoproteins, Genes, Mutation