SMPD1

The SMPD1 gene carries the instructions to make an enzyme called acid sphingomyelinase. This enzyme is found in lysosomes (small compartments in the cell that digest and recycle molecules) and is responsible for the conversion of a lipid (fat) called sphingomyelin into another type of lipid called ceramide. This lipid conversion is critical for the normal structure and function of cells and tissues.

One copy of this gene is inherited from each parent; however, only the gene inherited from a person's mother (the maternal copy) is active. This parent-specific gene activation is called genomic imprinting. If the maternal copy of the SMPD1 gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene because the gene inherited from a person's father (the paternal copy) is inactive.

Niemann-Pick disease - caused by mutations in the SMPD1 gene

More than 100 mutations in the SMPD1 gene have been found to cause Niemann-Pick disease types A and B. Mutations that alter the SMPD1 gene generally cause a significant reduction or complete absence of acid sphingomyelinase activity in cells. This lack of enzyme activity leads to the accumulation of sphingomyelin, cholesterol, and other types of lipids within the cells and tissues of affected individuals. Mutations that cause the enzyme to be inactive tend to cause the more severe Niemann-Pick disease type A. Mutations that cause the production of a defective enzyme that retains some activity often cause the milder Niemann-Pick disease type B. A shortage of enzyme activity within cells allows lipids to accumulate, which disrupts normal cell function and leads to cell death.