摘要目的 观察2例谷氨酰胺-果糖-6-磷酸转氨酶1(GFPT1)相关性肢带型先天性肌无力综合征患者的临床、电生理及病理改变特点.方法 收集于2014年3月和2014年6月就诊于北京大学第一医院神经内科并诊断为GFPT1相关性肢带型先天性肌无力综合征的2例患者,回顾性分析2例患者的临床资料、实验室、电生理、肌肉病理及基因检查结果,总结本病的临床特点,并随访其治疗效果.结果 例1男性,16岁,活动后易疲劳10年.例2男性,9岁,活动后易疲劳6年.2例患者体检均显示四肢近端肌力Ⅳ级.例1血清肌酸激酶轻度升高(224 IU/L),例2正常.例1、例2腋神经3 Hz重复神经电刺激复合肌肉动作电位波幅分别递减46.9％、17.5％.2例患者血清乙酰胆碱受体抗体水平均正常,给予溴吡斯的明治疗后症状均得到明显改善.例1骨骼肌内可见肌纤维内大量管聚集,例2Ⅰ型肌纤维病理占优势.2例患者经GFPT1基因检查均存在2个复合杂合突变,例1分.别为p.Y367C和p.G564C,例2分别为p.G26S和p.V291I.结论 GFPT1相关性肢带型先天性肌无力综合征多为儿童期起病,以波动性肌无力、肢带型肌无力为主要表现,低频刺激下波幅递减、肌肉病理出现管聚集可作为诊断线索.胆碱酯酶抑制剂为治疗本病的首选药物.

abstractsObjective To describe clinical,neurophysiological and pathological features in 2 patients with glutamine-fructose-6-phosphate transaminase 1 (GFPT1)-related limb-girdle congenital myasthenic syndrome.Methods We recruited two patients diagnosed as GFPT1-related limb-girdle congenital myasthenic syndrome in Peking University First Hospital in March and June 2014 respectively.Then we collected clinical,laboratory,neurophysiological,neuropathological and genetic data of the 2 patients to characterize the disease features.We also followed up the two patients to evaluate therapeutic effects.Results Case 1 was a sixteen years old boy complaining of exercise related fatigue for 10 years.Case 2 was a nine years old boy complaining of exercise related fatigue for 6 years.Both patients revealed mild proximal weakness during physical examinations.The level of serum creatine kinase was 224 IU/L in case 1 and within normal range in case 2.Repetitive nerve stimulation with 3 Hz at axillary nerve revealed decremental response of the main compound muscle action potential amplitude,which was 46.9％ in case 1 and 17.5％ in case 2.Anti-acetylcholine receptor antibody was not detected in both cases.Both of them responded well to oral pyridostigmine bromide.Muscle biopsies and GFPT1 gene analysis were performed in 2 cases.Muscle biopsy revealed massive tubular aggregates within muscle fibers in case 1 and type 1 fiber predoninance in case 2.GFPT1 showed 2 compound heterozygous mutations in patient 1 with p.Y367C and p.G564C,and in patient 2 with p.G26S and p.V291I respectively.Conclusions Childhood onset,fluctuating limb girdle weakness,decrement on low frequency repetitive nerve stimulation,tubular aggregates on muscle pathology could be considered as the diagnostic clues for GFPT1-related limb-girdle congenital myasthenic syndrome.Cholinesterase inhibitors therapy could be used as the first choice in this disease.