112 ILAR Journal

Lysosomal storage diseases (LSDs) are inherited metabolic disorders caused by defi cient activity of a single lysosomal enzyme or other defects resulting in defi cient catabolism of large substrates in lysosomes. There are more than 40 forms of inherited LSDs known to occur in humans, with an ag-gregate incidence estimated at 1 in 7,000 live births. Clinical signs result from the inability of lysosomes to degrade large substrates; because most lysosomal enzymes are ubiqui-tously expressed, a defi ciency in a single enzyme can affect multiple organ systems. Thus LSDs are associated with high morbidity and mortality and represent a signifi cant burden on patients, their families, the health care system, and soci-ety. Because lysosomal enzymes are traffi cked by a mannose 6-phosphate receptor mechanism, normal enzyme provide