Metabolic Medicine, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
J Mother Child. 2020 Oct 2;24(2):3-8. doi: 10.34763/jmotherandchild.20202402si.2001.000002.
Pompe disease is an autosomal recessive lysosomal glycogen storage disorder caused by the deficiency of acid alpha-glucosidase and subsequent progressive glycogen accumulation due to mutations in the GAA gene. Pompe disease manifests with a broad spectrum of disease severity, ranging from severe infantile-onset diseases such as hypotonia and hypertrophic cardiomyopathy to late-onset diseases such as myopathy and respiratory compromise. The diagnosis requires demonstration of deficiency of the lysosomal acid alpha-glucosidase enzyme, which can be assayed in dried blood spot or liquid blood samples, together with supportive biomarker tests, and confirmed with molecular genetic analysis. Targeted screening of at-risk populations and universal newborn screening can result in earlier diagnosis and enable earlier treatment initiation, which result in the potential improvement of clinical outcomes. Disease-modifying treatment with enzyme replacement therapy has partially altered the natural history of the disease, but more efficacious novel therapies are under evaluation including second-generation enzyme replacement therapies, molecular chaperones and gene therapy approaches. Long-term survivors with Pompe disease are now manifesting novel aspects of the disease including widespread vascular disease, smooth muscle and central nervous system involvement, and these emerging phenotypes will require additional specific therapeutic approaches.
庞贝病是一种常染色体隐性溶酶体糖原贮积症，由 GAA 基因突变导致酸性α-葡萄糖苷酶缺乏，进而引起糖原进行性积累。庞贝病的临床表现具有广泛的疾病严重程度，从轻度婴儿起病的疾病（如肌张力低下和肥厚型心肌病）到晚发型疾病（如肌病和呼吸功能障碍）。诊断需要证明溶酶体酸性α-葡萄糖苷酶的缺乏，这可以通过干血斑或液体血样进行检测，同时结合支持性生物标志物检测，并通过分子遗传学分析进行确认。对高危人群进行靶向筛查和普遍新生儿筛查可以实现更早的诊断，并更早开始治疗，从而有可能改善临床结局。酶替代疗法的疾病修饰治疗部分改变了疾病的自然史，但正在评估更有效的新型疗法，包括第二代酶替代疗法、分子伴侣和基因治疗方法。长期存活的庞贝病患者现在表现出疾病的新方面，包括广泛的血管疾病、平滑肌和中枢神经系统受累，这些新出现的表型将需要额外的特定治疗方法。
