【作者】 杨娟； 操基清； 刘振华； 詹益鑫； 梁颖茵； 莫桂玲； 李亚勤； 孙毅明； 李敏子； 利婧； 张成；

【Author】 YANG Juan;CAO Ji-qing;LIU Zhen-hua;ZHAN Yi-xin;LIANG Ying-yin;MO Gui-ling;LI Ya-qin;SUN Yi-ming;LI Min-zi;LI Jing;ZHANG Cheng;Department of Neurology,Zhujiang Hospital of Southern Medical University;Department of Neurology,the First Affiliated Hospital,Sun Yat-sen University;Guangzhou Kingmed Diagnostic Center Co.Ltd;Department of Health,the First Affiliated Hospital,Sun Yat-sen University;

【机构】 南方医科大学珠江医院神经内科； 中山大学附属第一医院神经科； 广州金域医学检验中心有限公司； 中山大学附属第一医院保健科；

【摘要】 目的分析4个家系7例晚发型糖原贮积病Ⅱ型患者之临床特点和基因型,以提高对该病的认识。方法收集患者临床资料,并行酸性α-葡糖苷酶（GAA）基因突变分析。结果7例患者分别来自4个家系,年龄13³1岁、发病年龄6¹7岁、初诊年龄12²9岁、明确诊断年龄12³0岁;首发症状为肢带肌萎缩、无力,酸性α-葡糖苷酶活性0⁵.27 nmol（/mg·h）。GAA基因突变分析共发现14种突变,其中2种为新突变位点（Q81X和c.1355₁356del C）、2种假缺陷等位基因位点（G576S和E689K）、8种多态性位点和2种已知的致病突变位点（W746C和D645E）。结论中国大陆地区对糖原贮积病Ⅱ型之诊断时间存在明显的延误,提高医务人员的认识和理解将有助于改善患者预后。在明确诊断糖原贮积病Ⅱ型或判断预后时,应结合临床病史、酸性α-葡糖苷酶活性检测和GAA基因突变分析。糖原贮积病Ⅱ型之临床表型具有异质性,在GAA基因型相同的情况下,同一家系的不同个体间可存在疾病进程和严重程度的差异。更多还原

【Abstract】 Objective In order to make a well understanding on glycogen storage disease type Ⅱ（GSD Ⅱ）,this paper explored clinical features and genetic analysis of 7 patients with late-onset glycogen storage disease type Ⅱ.Methods Clinical data of 7 patients with late-onset glycogen storage disease typeⅡ were collected and acid α-glucosidase（GAA） gene sequencing was performed.Results Seven patients who belong to 4 families were at the age of 13-31 years old.The first symptom occurred at 6-17 years old,and the age at first and definitive diagnosis was 12-29 and 12-30 years old,respectively.The initial symptoms were mostly related to limb girdle muscular atrophy and weakness.The GAA activity ranged from 0 to 5.27 nmol/（mg·h）.Sequencing analysis revealed 14 sequence variants,including 2 novel mutations（Q81 X and c.1355₁356 delC）,2 pseudodeficiency alleles（G576 S and E689 K）,8 polymorphic loci,and 2 sequence variants previously related with glycogen storage disease type Ⅱ pathogenesis（W746 C and D645 E）.Conclusions Due to the apparently diagnostic delay,prognosis of patients with glycogen storage disease type Ⅱ could be improved by increasing the clinician’s awareness of the disease.It is essential to combine clinical history with GAA activity and GAA gene analysis when we make a definitive diagnosis of glycogen storage disease type Ⅱ.Though siblings share the same set of GAA mutations,the phenotype regarding the course and severity of disease could vary substantially.更多还原