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13 ~ 31 岁、发病年龄6 ~ 17 岁、初诊年龄12 ~ 29 岁、明确诊断年龄12 ~ 30 岁；首发症状为肢带肌萎缩、无力，酸性α-葡糖苷酶活性0 ~ 5.27 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.1355_1356delC）、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。
关键词:
糖原贮积病Ⅱ型,
α葡糖苷酶类,
基因,
突变
Abstract: Objective In order to make a well understanding on glycogen storage disease typeⅡ (GSDⅡ), this paper explored clinical features and genetic analysis of 7 patients with late-onset glycogen storage disease typeⅡ. Methods Clinical data of 7 patients with late-onset glycogen storage disease type Ⅱ 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 (Q81X and c.1355_1356delC), 2 pseudodeficiency alleles (G576S and E689K), 8 polymorphic loci, and 2 sequence variants previously related with glycogen storage disease type Ⅱ pathogenesis (W746C and D645E). 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.
Key words:
Glycogen storage disease type Ⅱ,
Alpha-glucosidases,
Genes,
Mutation
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. 七例晚发型糖原贮积病Ⅱ型患者临床特征及基因突变分析[J]. 中国现代神经疾病杂志, 2014, 14(5): 405-410.
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. Clinical features and genetic analysis of 7 patients with late-onset glycogen storage disease typeⅡ[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2014, 14(5): 405-410.