sphingomyelin phosphodiesterase 1
The SMPD1 gene provides instructions for making an enzyme called acid sphingomyelinase. This enzyme is found in lysosomes, which are small compartments in the cell that digest and recycle molecules. Acid sphingomyelinase is responsible for the conversion of a fat (lipid) called sphingomyelin into another type of lipid called ceramide. Sphingomyelin also binds (attaches) to a fat called cholesterol and helps to form other lipids that play roles in various cell processes. The formations of these lipids is critical for the normal structure and function of cells and tissues.
At least 175 mutations in the SMPD1 gene have been found to cause Niemann-Pick disease types A and B. These types of Niemann-Pick disease are characterized by a buildup of fat within cells that leads to lung disease and enlargement of the liver and spleen (hepatosplenomegaly). Type A is more severe and is characterized by severe neurological impairment in early childhood.
SMPD1 gene mutations that cause complete loss of enzyme function tend to cause Niemann-Pick disease type A. In the Ashkenazi (eastern and central European) Jewish population, three mutations are responsible for about 90 percent of all Niemann-Pick disease type A cases. Mutations that lead to the production of an enzyme that retains some activity often cause Niemann-Pick disease type B. A reduction in enzyme activity within cells allows sphingomyelin to accumulate in cells. The accumulation of this lipid causes cells to malfunction and eventually die. Over time, cell loss impairs function of tissues and organs including the brain, lungs, spleen, and liver in people with Niemann-Pick disease types A and B.
- acid sphingomyelinase
- sphingomyelin phosphodiesterase 1, acid lysosomal
- sphingomyelin phosphodiesterase 1, acid lysosomal (acid sphingomyelinase)