| Popis: |
Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease, in which the accumulation of undegraded glycosaminoglycans leads to a progressive multisystem disease. Despite available treatments, a significant residual disease burden is seen in patients. This thesis contains three parts, focusing on different aspects of residual disease. In the first part, methods for an early and accurate diagnosis and classification are sought. This will provide an opportunity for start of treatment in an early phase of the disease, which will provide a better chance of prevention of clinical manifestations. In the second part the effect of the currently available enzyme replacement therapy and subsequent antibody formation on biochemical correction is described. These parameters are furthermore correlated with the presence and severity of sleep apnea. A modified enzyme replacement therapy is evaluated for improvement of accumulation of glycosaminoglycans in the central nervous system. In the final part, the focus lies on skeletal manifestations of the disease. Both the radiological trends and optimal treatment strategies for a characteristic form of hip dysplasia are described, contributing to optimizing clinical care for patients with MPS I. |
