Lysosomes are membrane-delimited, hydrolase rich organelles responsible for the degradation of biological macromolecules. They also play an important part in processing essential metabolites. A genetic defect in a protein responsible for maintaining the lysosomal system results in the accumulation within lysosomes of partially degraded molecules, the initial step in the process leading to a lysosomal storage disease. The defective protein may be a luminal lysosomal enzyme or protein cofactor, a lysosomal membrane protein or a protein involved in the post-translational modification or transport of lysosomal proteins. Lysosomal storage diseases (LSD’s) comprise a diverse group of monogenetic disorders with complex clinical phenotypes that include both systemic and central nervous system pathologies. They encompass greater than 40 distinct inherited metabolic diseases and have a collective incidence of 1 in 7000–8000 live births. LSD’s are progressive and may present at any age affecting any number of tissues and organ systems. Most of the genes for the lysosomal proteins have been cloned, permitting mutation analysis in individual cases. This information can be used for genotype/phenotype correlation, genetic counseling and the selection of patients for novel forms of therapy, such as substrate deprivation or dispersal, enzyme replacement, bone-marrow transplantation and gene transfer. In this article, we will briefly review the cell biological and clinical features of these diseases and discuss the progress towards the development of effective treatments.
Loading....