糖原贮积症Ⅱ型一家系的临床特点及基因突变分析  

Clinical features and genetic analysis of one pedigree of glycogen storage disease type

作　　者：操基清[1] 张成[1] 刘友章[2] 黄永兰 刘丽 杨娟[1] 李亚勤[1] 冯善伟 利婧[1] 佘世峰[2] 

机构地区：[1]中山大学附属第一医院神经科,广州510080 [2]广州中医药大学第一附属医院肛肠科 [3]广州市妇女儿童医疗中心内分泌科 [4]广州市人口和计划生育科学研究所

出　　处：《中华神经科杂志》2013年第1期32-36,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金面上项目资助项目（30870851）;国家自然科学基金省部联合重点资助项目（U1032004）;广东省人口和计划生育委员会重点资助项目（2010002）

摘　　要：目的报道1个糖原贮积症Ⅱ型家系并总结其临床特征，提高临床医生对糖原贮积症Ⅱ型早期诊断重要性的认识。方法收集一家系3例青少年型糖原贮积症Ⅱ型患者的临床资料，进行外周血酸性α葡糖苷酶（acidalphaglucosidase，GAA）活性和GAA基因检测。结果患者分别为男性1例、女性2例，Ⅱ1、Ⅱ3、Ⅱ7发病年龄分别为16、17和12岁，均出现进行性四肢近端无力，Ⅱ7和Ⅱ3均较早出现严重的呼吸肌无力，呼吸功能衰竭，依赖呼吸机支持，Ⅱ1也在病程早期表现出呼吸肌无力。Ⅱ7和Ⅱ3的肌酸激酶轻中度升高，符合青少年型糖原贮积症Ⅱ型的临床表现。3例患者外周血白细胞GAA活性均明显低于健康人群。GAA基因测序示3例患者均存在GAA基因的复合杂合突变，即外显子2的无义突变c．241C〉T（P．Gln81X）和外显子16的错义突变c．2238G〉C（P．Trp746Cys）。结论GAA活性和GAA基因检测对早期诊断糖原贮积症Ⅱ型患者非常重要，且便于遗传咨询及产前诊断。Objective In order to improve the clinician＇ s awareness of the importance of early diagnosis of glycogen storage disease type Ⅱ , we reported a rare pedigree of glycogen storage disease type II and summarized the clinical characteristics of it. Methods Clinical data of three patients in a family with juvenile glycogen storage disease type I] were collected and peripheral blood acid alpha-glucosidase （GAA） activity testing and GAA gene sequencing were performed. Results Three patients （one male and two females） with typical clinical manifestations of the glycogen storage disease type Ⅱ were identified. They all manifested progressive proximal limb weakness with age at onset being 16,17 and 12 years old in Ⅱ1, Ⅱ 3 and Ⅱ 7,respectively. Ⅱ7 and Ⅱ 3 manifested severe respiratory muscles weakness, respiratory failure and ventilator dependency survival at an earlier onset. Ⅱ 1 also manifested moderate respiratory muscles weakness early. The increase of creatine kinase in Ⅱ 7 and 113 was mild to moderate. The GAA activity of the three patients was significantly lower than normal. A nonsense mutation of c. 241C 〉 T （p. GlnglX）in exon 2 and a missense mutation of c. 2238G 〉 C（ p. Trp746Cys） in exon 16 were detected in all of the three patients. Conclusion GAA activity and GAA genetic testing are very important for early diagnosis of glycogen storage disease type Ⅱ and are helpful for clear diagnosis, carriers, genetic counseling and prenatal diagnosis.

关 键 词：糖原贮积病Ⅱ型 早期诊断 α葡糖苷酶类 突变 系谱 

分 类 号：R589.1[医药卫生—内分泌]