Some inherited lysosomal enzyme defects with special reference to the liver and prospects for their control

Lysosomes are subcellular organelles which contain hydrolytic enzymes. These enzymes catalyse the degradation of macromolecules which are: I. taken into the cell by endocytosis; II. derived from the cells own structural components by autophagy; III. unused secretory products in the case of exocrine or endocrine cells. Each of the lysosomal storage diseases is due to the mutation of a gene which directs the synthesis of a specific lysosomal enzyme. This alters the catalytic activity of the enzyme and specific, incompletely degraded, macromolecules accumulate. The lysosomal enzymes pass from cell to cell by a combination of exocytosis and endocytosis, and this makes enzyme replacement therapy potentially feasible. The on-going trial of fibroblast transplantation as a means of enzyme replacement for the treatment of Pfaundler-Hurler disease in the author's laboratory, is briefly described.