晚发型糖原贮积病Ⅱ型临床、肌肉组织病理学及分子生物学特征分析  

Clinical,muscle pathology and molecular biological features of late-onset glycogen storage disease typeⅡ

作　　者：吴世陶[1] 刘方[2] 石伟伟 张敏[1] 刘恒方[1] WU Shi-tao;LIU Fang;SHI Wei-wei;ZHANG Min;LIU Heng-fang(Department of Neurology,The Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,He'nan,China;Department of Nursing,The Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,He'nan,China)

机构地区：[1]郑州大学第五附属医院神经内科,450052 [2]郑州大学第五附属医院护理部,450052

出　　处：《中国现代神经疾病杂志》2021年第6期466-472,共7页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：河南省医学科技攻关计划省部共建项目(项目编号:SB201901056)。

摘　　要：目的总结晚发型糖原贮积病Ⅱ型(GSDⅡ)的临床表现、肌肉组织病理学和分子生物学特征。方法与结果选择2013年1月至2020年1月在郑州大学第五附属医院诊断与治疗的5例晚发型GSDⅡ型患者,临床主要表现为抬头无力、四肢近端肌无力、肌张力降低、不耐受疲劳和呼吸困难,酸性α葡糖苷酶(GAA)活性均明显降低。5例患者肌肉组织HE染色显示多数肌纤维内可见大小不一、数量不等、形态不规则的空泡样变性;改良Gomori三色染色可见空泡内有大量蓝紫色颗粒沉积;高碘酸-雪夫染色显示4例空泡内糖原成分增多,1例空泡内糖原成分流失。GAA基因检测显示,5例患者共检出9个变异位点,4例为复合杂合突变,分别来源于父亲和母亲,分别为c.13201322delGAT(p.Met440del)缺失突变、c.2331G>C(p.Thr777Thr)同义突变、c.2237G>A(p.Trp746^(*))无义突变、c.877G>A(p.Gly293Arg)错义突变、c.2238G>C(p.Trp746Cys)错义突变、c.784G>A(p.Glu262Lys)错义突变、c.2014C>T(p.Arg672Trp)错义突变和c.2332-2A>G剪切突变;1例为c.1432G>A(p.Gly478Arg)纯合突变,来源于母亲。其中,c.2331G>C、c.1432G>A和c.2332-2A>G系国内外首次报道。结论晚发型GSDⅡ型患者临床表现主要为四肢近端肌无力和呼吸困难,血清GAA酶活性明显下降,肌肉组织病理学具有特征性,GAA基因变异主要为复合杂合突变,其中,c.2331G>C、c.1432G>A和c.2332-2A>G为新发变异,扩展了GAA基因变异谱。Objective To summarize the clinical,muscle pathology and molecular biological features of late-onset glycogen storage disease typeⅡ(GSDⅡ).Methods and Results Five patients with late-onset GSDⅡdiagnosed and treated in The Fifth Affiliated Hospital of Zhengzhou University from January 2013 to January 2020 were selected.The main clinical manifestations of 5 patients were weakness of raising the head,weakness of the proximal extremities,decreased muscle tone,fatigue intolerance,and dyspnea.The activity of acidα-glucosidase(GAA)was significantly reduced.HE staining of muscular tissues in 5 patients showed vacuole-like changes of different sizes,different numbers,and irregular shapes in most muscle fibers.Modified Gomori trichrome(MGT)staining showed a large number of blue and purple particles deposited in the vacuole.Periodic acid-Schiff(PAS)staining showed the glycogen content in the vacuoles were increased in 4 cases,and the glycogen content in the vacuoles were lost in one case.GAA gene testing showed that 9 mutations were detected in 5 patients,and 4 cases were compound heterozygous mutations,which were derived from father and mother respectively.The c.13201322 delGAT(p.Met440 del)was a deletion mutation,c.2331 G>C(p.Thr777 Thr)was a synonymous mutation,c.2237 G>A(p.Trp746^(*))was a nonsense mutation,c.877 G>A(p.Gly293 Arg)was a missense mutation,c.2238 G>C(p.Trp746 Cys)was a missense mutation,c.784 G>A(p.Glu262 Lys)was a missense mutation,c.2014 C>T(p.Arg672 Trp)was a missense mutation,and c.2332-2 A>G was a splicing mutation.One case was homozygous mutation of c.1432 G>A(p.Gly478 Arg),which originated from the mother.Among them,c.2331 G>C,c.1432 G>A and c.2332-2 A>G were reported for the first time at home and abroad.Conclusions The clinical manifestations of late-onset GSDⅡare weakness of proximal limbs and dyspnea.The activity of GAA in peripheral serum is decreased significantly.Muscle tissue pathology is characteristic.GAA gene mutations are mainly compound heterozygous mutation,c.2331 G>C,c.1432 G>

关 键 词：糖原贮积病Ⅱ型 晚发性障碍 α葡糖苷酶类 病理学 分子生物学 基因 突变 

分 类 号：R596.1[医药卫生—内科学]