My PhD project investigates the evolving clinical phenotype of patients with classic infantile Pompe disease who receive enzyme replacement therapy (ERT) and survive into childhood and beyond. Pompe disease is a rare lysosomal storage disorder caused by deficiency of the enzyme acid α-glucosidase, leading to glycogen accumulation in muscle and brain tissue. While ERT significantly improves survival and motor outcomes in classic infantile patients, many continue to show residual muscle weakness and signs of central nervous system (CNS) involvement, areas that are not yet fully understood. This research aims to better characterize these features and compare them to those seen in patients with the milder, late-onset form of the disease. The project focuses on two key areas: CNS involvement, studied through advanced brain imaging and neuropsychological testing; and muscle involvement, examined using clinical assessments and quantitative muscle MRI. The project is embedded within the longstanding Pompe research program at the Erasmus MC, Center for Lysosomal and Metabolic Diseases, the national referral center for Pompe disease, providing access to a unique patient cohort. Muscle MRI studies are conducted in collaboration with the C.J. Gorter Center for High Field MRI at Leiden University Medical Center (LUMC), a leading center for advanced imaging. This work supports more targeted treatments and improved long-term care.