Gaucher disease: pathological mechanisms and modern management.

Gaucher disease, the most common lysosomal storage disorder, is caused by the defective activity of the lysosomal enzyme, acid-beta-glucosidase (GlcCerase), leading to accumulation of glucosylceramide (GlcCer), particularly in cells of the macrophage lineage. Nearly 200 mutations in GlcCerase have been described, but for the most part, genotype-phenotype correlations are weak, and little is known about the down-stream biochemical changes that occur upon GlcCer accumulation that result in cell and tissue dysfunction. In contrast, the clinical course of Gaucher disease has been well described, and at least one treatment is available, namely enzyme replacement therapy. One other treatment, substrate reduction therapy, has recently been marketed, and others are in early stages of development. This review, after discussing pathological mechanisms, evaluates the advantages and disadvantages of existing therapies.