Between 40 and 50 lysosomal storage disorders are known at present. Fine details of the pathogenic process involved are in general not known. This overview highlights the basic principles of lysosomal pathogenesis and the clinical consequences of defective genes involved in lysosomal functions. The subject is discussed in the context of the possibility of prevention and reversal of cellular and organ damage by enzyme replacement therapy. Also presented is a mechanical model for the muscle pathology observed in Pompe disease. Direct mechanical effects of the non-contractile inclusions - glycogen-loaded lysosomes - seem to be a key factor in the loss of force during both early and late stages of the disease. Conclusion: Each lysosomal storage disorder and each patient with a given lysosomal disorder has unique molecular, pathological and clinical features. But, the order of pathological events is largely the same. Mutations in a gene cause lysosomal dysfunction which, in turn, results in cellular pathology affecting organ structure and function. Clinical symptoms are the ultimate manifestation. The reversibility of symptoms with enzyme replacement therapy will vary according to the disease, as well as the nature and stage of organ pathology.

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Acta Paediatrica: promoting child health
Department of Clinical Genetics

Reuser, A., & Drost, M. (2006). Lysosomal dysfunction, cellular pathology and clinical symptoms: Basic principles. In Acta Paediatrica: promoting child health (Vol. 95, pp. 77–82). doi:10.1080/08035320600618957