核黄素反应性脂质沉积性肌病伴感觉共济失调性神经病3例报告

目的研究核黄素反应性脂质沉积性肌病伴感觉共济失调性神经病的临床、电生理、病理和基因改变特点。方法 3例男性患者来自2个家系,其中2例为兄弟,发病年龄41～43岁,主要症状是四肢肌无力,伴随双足麻木和行走不稳。查体发现四肢近端肌力下降、末梢性感觉丧失和Romberg征阳性。3例患者的血尿代谢筛查均提示存在血多种脂酰肉碱水平升高和尿戊二酸水平增高。3例患者均进行了神经电生理、肌肉活检以及电子转移黄素蛋白脱氢酶(ETFDH)基因检查,2例进行腓肠神经活检。结果 3例患者的肌电图分别出现肌源性损害、可疑神经源性损害和无异常。3例患者的四肢感觉神经传导速度显著减慢或不能引出,运动神经传导速度仅在1例出现轻度减慢。3例患者的骨骼肌均可见肌纤维内脂肪滴显著增多,2例有个别破碎红纤维,2例出现小角状肌纤维。2例患者的腓肠神经均可见有髓神经纤维中-重度减少,伴随有髓神经纤维轴索变性和再生。3例患者均携带ETFDH基因的复合杂合突变,其中2兄弟为c.65A>G和c.242T>C,另1例为c.770A>G和c.1450 T>C。结论 ETFDH基因突变导致的核黄素反应性脂质沉积性肌病可以伴随感觉共济失调性神经病。

Riboflavin responsive lipid storage myopathy with sensory ataxic neuropathy:3 cases reports

Objective To report 3 cases of riboflavin responsive lipid storage myopathy with sensory ataxic neuropathy.Methods Three male patients were from 2 unrelated families,two of them being brothers.The ages of onset were from 41 to 43 years.All of them presented with limbs weakness,numbness in both feet and walking unsteadily.Physical examination showed proximal weakness with distal sensory loss and Romberg’signs.High serum acyl-carnitine level and glutaric aciduria were detected in all cases.Electromyography and nerve conduction velocity studies,muscle biopsies and ETFDH gene analysis were performed in all cases.Sural nerve biopsies were performed in 2 cases.Results Electromyography revealed myopathic pattern,neurogenic pattern and no abnormalities in 1 case respectively.Nerve conduction velocity studies showed sensory nerve action potentials were not evoked or the conduction velocities marked slow in all 3 cases,while mild slowing of motor conduction velocities were detected in only 1 case.Muscle biopsies showed numerous lipid droplets in the muscle fibers in 3 cases,RRF in 2 cases and angular fibers in 2 cases.Marked loss of myelinated fibers with axonal degeneration and regeneration could be seen in both sural nerves biopsies.ETFDH gene analysis identified all patients carrying compound heterozygous mutations,c.65A>G and c.242T>C in the 2 brothers and c.770A>G and c.1450 T>C in the third one.Conclusion Sensory ataxic neuropathy can be present in riboflavin responsive lipid storage myopathy associated with ETFDH gene mutations.