Musculoskeletal complications encountered in the lysosomal storage disorders

The lysosomal storage disorders are a heterogeneous group of inherited metabolic diseases resulting from defects in the degradation or transport of several distinct by-products of cellular turnover. The various subtypes are characterized by multi-systemic involvement; the wide range in patient ages at symptom onset is only partly explained by the underlying mutation(s). Neurodegenerative features and musculoskeletal complications are often seen in the most severe variants, and are features of the disease that have the most significant impact on patients' physical and functional well-being. Until recently, the care of affected individuals relied mainly on palliative or supportive measures. The introduction of therapies directed at correcting the primary defect (i.e., deficient enzyme activity) in several of these disorders has led to modification of the phenotype and natural history or disease course; however, clinical problems arising from brain and bone involvement remain major sources of morbidity. Factors that might influence therapeutic outcome include pre-existing pathology at the time of treatment initiation, drug access to tissues sites of pathology, and – in the case of enzyme therapy – antibody formation. Increasing understanding of the pathogenesis or relevant mechanism(s) of diseases is providing insights into additional therapeutic targets, enabling the potential for optimized patient outcomes with the use of adjunctive or supplemental agents. Physical and occupational therapy remain critical components of a comprehensive approach to patient care.

Key words: enzyme replacement therapy, Gaucher disease, hematopoietic stem cell transplantation, Hurler syndrome, lysosomal storage disorder, mucopolysaccharidosis