The disease is caused by a defect in housekeeping gene for lysosomal glucocerebrosidase (also known as beta-glucosidase, , ) on the first chromosome (1q22). The enzyme is a 55.6-kilodalton, 497-amino acid-long protein that catalyses the breakdown of glucocerebroside, a cell membrane constituent of red and white blood cells. In<unk>  disease, the enzyme is unable to function correctly and glucocerebroside accumulates. The macrophages that clear these cells are unable to eliminate the waste product, which accumulates in fibrils, and turn into<unk>  cells', which appear on light microscopy to resemble crumpled-up paper. The exact mechanism of neurotoxicity is not understood, but it is thought to involve a reaction to glucosylsphingosine. Different mutations in the GBA (beta-glucosidase) gene determine the remaining activity of the enzyme. In type I, there is some residual activity of the enzyme, accounting for the lack of neuropathology in this type. Although there is some correlation between genotype and phenotype, neither the amount of stored lipids, nor the residual enzyme activity correlates well with disease symptoms. This circumstance has called for alternative explanations accounting for disease symptoms including * jamming of the endo/lysosomal system * ER stress * altered lipid composition of membranes throughout the cell, including the plasma membrane, and consequent changes in the dynamic and signaling properties of the cell membrane * inflammation caused by cytokine secretion as a result of sphingolipid accumulation, and neurodegeneration caused by the accumulation of glucosylsphingosine, a neurotoxin Heterozygotes for particular acid beta-glucosidase mutations carry about a five-fold risk of developing Parkinson's disease, making this the most common known genetic risk factor for Parkinson's. Cancer risk may be increased, particularly myeloma. This is thought to be due to accumulation of glucosylceramide and complex glycosphingolipids. The role of inflammatory processes in<unk>  disease is poorly elucidated. However, sphingolipids are known to participate in inflammation and apoptosis, and markers of macrophage activation are elevated in people with<unk>  disease. These markers include angiotensin-converting enzyme, cathepsin S, chitotriosidase, and CCL18 in the blood plasma; and tumor necrosis factor alpha in splenic<unk>  cells (engorged macrophages).
Gaucher's disease
Glycogen storage disease type III
Glycogen storage disease type 0
Glycogen storage disease type IX
Glycogen storage disease type IV
Glycogen storage disease type I
Glycogen storage disease type II
Glycogen storage disease type VI