Neuromuscular Imaging and Phenotypical Variation in Pompe Disease

Pompe disease is a progressive metabolic myopathy. It is caused by a deficiency of the enzyme acid α-glucosidase and leads to glycogen accumulation, predominantly in skeletal muscle. All Dutch patients diagnosed with Pompe disease are referred to the ‘Center of Lysosomal and Metabolic Diseases’ at Erasmus MC University Medical Center, which makes it possible to study features of this orphan disease in a relatively large cohort. In this thesis the clinical heterogeneity, genotype-phenotype correlations and the role of modifiers within families with Pompe disease is described. In addition, laboratory diagnostics and imaging techniques were studied. Using lung MRI in combination with spirometry more insight was obtained into the function and strength of the respiratory muscles. It showed decreased displacement of the diaphragm in patients with Pompe disease. Using tonometry of the carotid-femoral pulse wave velocity, it was demonstrated that patients with Pompe disease had increased arterial stiffness, together with an increased blood pressure compared with controls. Additionally, it was shown that cardiac troponin T was elevated in the majority of patients as a result of skeletal muscle damage rather than myocardial damage. Finally, it was demonstrated that exercise training is safe and can serve as an adjuvant treatment in mildly affected patients with Pompe disease.