Clinical features, disease course, and effects of enzyme therapy in Pompe disease

Pompe disease is an autosomal recessive metabolic disorder whereby mutations in the GAA gene lead to the partial or total absence of the lysosomal enzyme acid α-glucosidase.

My thesis highlights the broad clinical spectrum of the disease in children and adults, describing unfamiliar features, such as ptosis, bulbar weakness, and scapular winging in a subset of patient, and investigates in detail the natural disease course, focusing on pulmonary, cardiac, and skeletal muscle involvement over time. The second part of the thesis focuses on the effects of enzyme-replacement therapy in children and adults; it shows that muscle function and respiratory function improve during the first years of treatment, but that there is considerable variability in treatment-response. The third section of the thesis reports on the construction of two new measurement instruments for use in Pompe disease, that enables us to better examine daily life activities.