What are Storage Diseases?

Lysosomal Storage Diseases

Lysosomal storage diseases (LSDs) are a group of 49 genetically inherited disorders that are characterized by a deficiency of one or more specific lysosomal enzymes which causes an accumulation of undigested material (macromolecules) inside the lysosome. This accumulation causes lysosomes to enlarge leading eventually to cell degeneration. This process results in accumulation of macromolecules in various tissues and organs of the body causing these organs to function less efficiently, resulting in progressive deterioration in physical and/or mental state, and eventually death. The cause of the enzyme deficiency in the lysosome is usually a mutation in a structural gene that codes, or creates, an individual lysosomal enzyme. Individual LSD's are classified as rare genetic disorders. However, when taken as a group, LSD's are far more common, with a prevalence rate of 1 per 7,700 births in some countries.

Normal Physiological Development of a Lysosomal Enzyme

The lysosome is an encapsulated single membrane organelle that houses as many as 40 digestive lysosomal enzymes. These enzymes are produced within every cell of the body in the area of the cell called the endoplasmic reticulum. This enzyme production which is under the influence of genes inherited from our parents. Lysosomal enzymes are incorporated into the lysosome and then function inside the lysosome. Once inside the lysosome, the lysosomal enzyme's job is to break down complex cellular compounds and foreign materials ingested by the cell (macromolecules) into simple products that are either utilized or excreted by the cell. To allow the enzyme to be taken up into the lysosome, it usually has a phosphate attached to it (phosphorylation). This phosphorylation enables the enzyme to bind to a specific manose-6phosphate (M6P) receptor on the surface of the lysosome and then enter the lysosome. Phosphorylation of an enzyme, therefore, functions as a key to allow the enzyme to enter the lysosome. Of the 49 lysosomal storage diseases, 48 utilize this M6P receptor system.

Lysosomal Enzyme Biology

In healthy cells, large molecules, such as glycolipids and glycogen, are broken down into functional units by lysosomal enzymes.

Lysosomal Pathology

In lysosomal storage disorders, the cell is unable to produce an enzyme responsible for the breakdown of large molecules which leads to cell death