General description

Glycogen storage disease type II, commonly known as Pompe disease, is a rare autosomal recessive disorder caused by mutations in the GAA gene, leading to deficient activity of the lysosomal enzyme acid alpha-glucosidase (GAA). Over 300 mutations have been identified, including missense, nonsense, splice-site, and frameshift variants, which disrupt glycogen metabolism within lysosomes. The residual enzyme activity determines disease severity: infantile-onset Pompe disease (IOPD) is associated with less than 1% GAA activity, while late-onset Pompe disease (LOPD) patients retain 2–40% activity. The inability to degrade lysosomal glycogen leads to widespread accumulation in tissues, including skeletal muscle, cardiomyocytes, and motor neurons, triggering cellular dysfunction and apoptosis.

Infantile-Onset Pompe Disease (IOPD)

IOPD manifests within the first year of life with severe hypotonia, hypertrophic cardiomyopathy, and feeding difficulties. Without treatment, progressive respiratory failure and cardiac complications lead to death by 12–18 months.

Late-Onset Pompe Disease (LOPD)

LOPD presents after 12 months of age, often in adolescence or adulthood, with proximal limb-girdle weakness, respiratory insufficiency, and hyperCKemia. Unlike IOPD, cardiomyopathy is rare, but diaphragmatic weakness leads to sleep-disordered breathing and eventual ventilator dependence.

References

1. Paoletti, Matteo, et al. "Multicentric retrospective evaluation of five classic infantile Pompe disease subjects under enzyme replacement therapy with early infratentorial involvement." Frontiers in Neurology 11 (2020): 569153.