中性脂肪沉积症合并肌病一家系

目的 报道1个中性脂肪沉积症合并肌病家系的临床和病理特点.方法 家系中同代2人发病,先证者为40岁女性,35岁出现缓慢发展的四肢肌肉无力和萎缩.其兄55岁,患先天性室间隔缺损,35岁出现双耳听力下降,45岁后出现四肢无力.对2例患者进行右肱二头肌活体组织检查,标本进行常规组织学、酶组织化学和电镜检查.对2例患者以及家系中其余3名健康成员进行三酯酰甘油水解酶-2(PNPLA2)基因检查.结果 2例患者均出现肌纤维肥大和萎缩伴随结缔组织增生,在许多肌纤维内可见镶边空泡以及大量脂肪滴沉积.电镜下可见空泡内出现髓样小体及细丝样包涵体,在肌原纤维之间可见大量脂肪滴.2例患者的PNPLA2基因2号内含子第1个碱基存在G＞A突变(IVS2+1G＞A).3名健康成员无此突变.结论 PNPLA2基因的2号内含子IVS2+1G＞A新突变导致的中性脂肪沉积症合并肌病出现明显的骨骼肌损害,该病可以伴随听神经损害以及先天性心脏病.肌纤维出现大量脂肪滴沉积和镶边空泡可能对诊断该病具有提示意义.

Neutral lipid storage disease with myopathy: a family report

Objective To study the clinical,myopathological features in neutral lipid storage disease with myopathy (NLSDM) caused by a novel PNPLA2 mutation.Methods Two patients were siblings.The proband was a 40-year-old woman.She presented progressive limb weakness and muscle atrophy at 35 years old.Her 55-year-old brother presented deafness at 35 years old and limb weakness at 45 years old. He suffered from ventricular septal defect.Open biosies were performed on them and specimens were studied histologically enzymhistochemically.and ultrastructurally.All the exons of PNPLA2 gene were analyzed in the both patients and 3 healthy family individuals.Results Muscle biopsy in both patients revealed hypertrophy and atrophy of fibers with proliferation of connective tissue.There were numerous lipid droplets and plenty of rimmed vacuoles in the fibers.Electron microscopy revealed lipid droplets between sarcomeres as well as myelin figures.A single homozygous base substitution was detected at the beginning of intron 2(IVS2+1G＞A)of PNPLA2 in two patients.but not in the healthy family individuals. Conclusion The novel IVS2+1G＞A mutation of PNPLA2 causes NLSDM with prominent limb weakness.The disease may be associated with auditory nerve lesions and congenital heart disense.Rimmed vacuoles with lipid storage in the fibets might have indication for diagnosis of NLSDM.