摘要目的 报道7例糖原累积病Ⅱ型(GSDⅡ)的临床表现及α-1,4葡萄糖苷酶(GAA)基因突变特点.方法 2003-2011年在北京大学第一医院行肌肉活检的患者中有7例诊断为GSDⅡ.其中婴儿型1例,其主要症状为生后出现全身力弱、心脏扩大、呼吸困难和肝脏肿大；晚发型患者6例,发病年龄在1～29岁,主要表现为进展性肢体力弱,其中2例有呼吸肌受累.7例患者均伴随CK升高,5例肌电图呈肌源性损害,1例为神经源性损害.肌肉活检均发现肌纤维存在嗜碱性空泡,电镜检查发现大量膜性包裹的糖原.应用PCR产物直接测序法对患者进行GAA基因的所有外显子及其侧翼序列突变检测.对发现的新突变位点在100例正常对照中进行筛查.结果 7例GSDⅡ患者均存在GAA基因突变,共检测出11种点突变和1种缺失突变,其中p.P361L、p.P266S、p.R437C、p.R600C、p.W746S和p.W746*为文献已经报道的突变,p.R168Q、p.R168P、p.E521V、p.R594H和c.827_845del为尚未报道的新突变类型.除p.R168Q在2例正常对照中检测到外,其余新突变均未发现正常携带者.7例GSDⅡ患者携带的突变各不相同,仅p.P361L和p.W746 *出现在两例患者中.结论 我国GSDⅡ患者存在较多新发突变,提示该病可能具有较多个体化突变.p.P266S、p.P361L和p.R437C突变可能与临床晚发型的GSDⅡ有一定相关性.

abstractsObjective To explore the clinical features and acid alpha-glucosidase (GAA) gene mutations of Chinese patients with glycogen storage disease type Ⅱ (GSD Ⅱ).Methods Seven patients with GSD Ⅱ were diagnosed by muscle pathology examination at Department of Neurology,Peking University First Hospital from 2003 to 2011.One patient with infant-onset presented development retardation,generalized muscle weakness,dyspnea,cardiomegaly and hepatomegaly.Six cases were of late-onset ranging from 1 to 29 years.Their main clinical features included progressive muscle weakness.Two patients developed respiratory insufficiency.Increased serum creatine kinase was detected in all of them.Electromyography studies showed myopathic (n =5) and neuropathic (n =1) changes.Muscle biopsies showed basophilic vacuoles in muscle fibers containing a large amountsof glycogen on electron microscopy.GAA gene mutation was detected by direct sequencing of polymerase chain reaction (PCR) product.Novel mutations were screened in 100 normal controls.Results GAA gene mutations were found in all of them,including 10 point mutations and 1 frameshift deletion.Six mutations (p.P361 L,p.P266S,p.R437C,p.R600C,p.W746S and p.W746 *) have been reported before.And five novel mutations (p.R168Q,p.R168P,p.E521V,p.R594H and c.827_845del) were found in this study.None of these novel mutations were found in 100 normal controls except for p.R168Q mutation in two normal controls.p.P361L and p.W746 * were detected in two unrelated GSD Ⅱ patients while other mutations were carried by only one patient.Conclusion In our study,we found several novel GAA mutations in Chinese patients with GSD Ⅱ.No hot spot mutation of GAA gene existed in our patient group.However,p.P266S,p.P361L and p.R437C might be associated with late-onset GSD Ⅱ.