Are there useful biochemical markers of disease activity in lysosomal storage diseases?

The primary biochemical consequence of a defect in a gene encoding a functional component of the lysosomal system is disruption of the catabolism or processing of macromolecules in the lumen of the lysosome. Transport of the resulting digestion products through the lysosomal membrane may also be affected. This leads to the accumulation of specific metabolites within the lysosomes of affected cells. The nature of these storage products depends upon the functional protein affected and the cell type. The accumulation of storage products is progressive and leads to hypertrophy of the lysosomal system, the hallmark of lysosomal storage diseases (LSDs). Subsequent cell necrosis or, possibly, exocytosis results in the appearance in body fluids of the storage products and components of the lysosomes at much higher concentrations than seen in normal unaffected individuals. Measurement of these increased levels of metabolites and proteins provides disease-specific and generic biochemical markers for LSDs. Secondary changes in metabolism and cellular function may also produce characteristic changes in the levels of metabolites or proteins, which can also be used as markers of the disease process. Although the rate of appearance of these biochemical markers in an individual will depend upon the underlying mutation in the gene and on other genetic and environmental factors, it provides a good indicator of the progression of the disease. As the novel forms of treatment being developed may reverse the hypertrophy of the lysosomal system, biochemical markers could also be used to monitor the reversal of pathology and the efficacy of treatment.