| 摘要: |
| 目的:总结5 例婴儿型糖原贮积症Ⅱ型(GSD Ⅱ)死亡病例的临床及遗传学资料,提高对该病的诊疗水平。方法:回顾性
分析我院诊治的5 例婴儿型GSD Ⅱ患儿的临床资料,利用基因测序进行遗传学分析,对突变基因的编码蛋白质结构进行预测
及功能分析,总结该病的临床及基因学特征。结果:5 例患儿均1 岁内发病,平均发病年龄3. 4 个月,平均就诊年龄4. 4 个月,平
均确诊年龄6. 6 个月,主要临床表现为心肌肥厚、发育落后、肌力低下、左心室收缩功能下降等;溶酶体酸性α-葡萄糖苷酶
(GAA)活性均下降,均为Chr17 GAA 基因复合杂合突变。共有10 个突变位点:错义突变5 个,无义突变3 个,缺失框移突变
2 个;其中2 个为未见报道的突变,分别为c. 1683C>A(p. Ser561Arg) 和c. 1780C>A(p. Arg594Ser)。突变基因编码蛋白结构预
测显示,5 个突变位点出现了截断蛋白,5 个错义突变导致蛋白结构改变及氢键异常。结论:婴儿型GSD Ⅱ是一种罕见的严重
神经肌肉疾病,发病早,病死率高。GAA 基因突变致GAA 活性下降是GSD Ⅱ的遗传学病因;提高临床医生对疾病的认识,早期
诊断并行重组人GAA 酶替代疗法(ERT)可治疗GSD Ⅱ。 |
| 关键词: 糖原贮积症Ⅱ型 GAA 基因 心肌肥厚,蛋白结构 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2025.07.007 |
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| 基金项目: |
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| Clinical Analysis on 5 Cases of Infantile Glycogen Storage Disease Type Ⅱ Caused by GAA Gene Mutation |
| Fan Yazhen, Zhao Jianchuang, Li Fan, Huang Xianjie, Wang Na, Qiao Junying |
| ((The Third Affiliated Hospital of
Zhengzhou University, Zhengzhou 450052, China)) |
| Abstract: |
| Objective: To summarize the clinical and genetic data of 5 dead cases of infantile glycogen storage disease type Ⅱ (GSD Ⅱ),
and improve the level of diagnosis and treatment. Methods: Clinical data of 5 cases of infantile GSD Ⅱ in our hospital were
retrospectively analyzed. Genetic analysis was performed by gene sequencing, and the structure of the protein encoded by the mutant
gene was predicted and its function was analyzed. The clinical and genetic characteristics of the disease were summarized. Results: All
the 5 children developed the disease within 1 year of age. The average age of onset was 3. 4 months, the average age of visit was 4. 4
months, and the average age of diagnosis was 6. 6 months. The main clinical manifestations included myocardial hypertrophy, delayed
development, low muscle strength, and decreased left ventricular systolic function. Acid α glucosidase ( GAA) enzyme activity
decreased significantly in 5 patients, all of which were Chr17 GAA gene complex heterozygous mutations, with a total of 10 mutation
sites, including 5 missense mutations, 3 nonsense mutations, and 2 missing frame shift mutations. And 2 mutation sites were unreported
mutations, respectively c. 1683C>A (p. Ser561Arg) and c. 1780C>A (p. Arg594Ser). The structural prediction of the encoded protein
of the mutated gene showed that there were truncated proteins at 5 mutation sites, and 5 missense mutated genes resulted in protein structural changes and hydrogen bond abnormalities. Conclusion: Infantile GSD Ⅱ is a rare and severe neuromuscular disease with early
onset and high mortality. The genetic cause of GSD Ⅱ is the decrease of GAA enzyme activity caused by GAA gene mutation. Awareness
of the disease should be raised among clinicians, and early diagnosis combined with recombinant human GAA enzyme replacement
therapy (ERT) could treat GSD Ⅱ. |
| Key words: glycogen storage disease type Ⅱ GAA gene myocardial hypertrophy protein structure |
