Niemann-Pick disease

background

Niemann-Pick disease (NPD) interferes with the breakdown of lipids (fats) and cholesterol in the body in a way that causes harmful amounts of lipids to build up in the spleen, liver, lungs, bone marrow, and brain.
NPD belongs to a group of inherited disorders known as leukodystrophies, or lipid storage disorders.
NPD is a relatively rare disease: the incidence of NPD type A and B is 1 in 250,000, and NPD type C affects one out of every 150,000 live births. However, certain populations may be affected more frequently by NPD.
There are five identified types of NPD: type A, type B, type C, type D, and type E.
NPD types A and B, also called type I NPD, are caused by low levels of an enzyme called acid sphingomyelinase, which is required to break down a lipid called sphingomyelin. Sphingomyelin is found in all cells in the body. When sphingomyelin is not metabolized properly, it builds up in cells, resulting in organ failure.
NPD type A occurs in infants and primarily affects the brain and liver. People with NPD type A rarely survive beyond 18 months of age.
Symptoms of NPD type B usually develop in the preteen years and affect the liver, lung, and spleen. Lung infections are common, and overall growth is impaired. Unlike NPD type A, the brain is not affected in NPD type B.
NPD types C and D, also called type II NPD, are characterized by a defect that disrupts the movement of cholesterol between brain cells.
NPD types C and D may appear anytime between infancy and adulthood. People with NPD types C or D have only moderate enlargement of the spleen and liver, but brain damage may be extensive.
NPD type D has only been identified in the French-Canadian population of Nova Scotia and is believed to be a form of NPD type C.
NPD type E occurs in adults and is extremely rare. Symptoms include swelling of the spleen and neurological problems.

Related Terms

Acid sphingomyelinase deficiency, DAF syndrome, defective cholesterol metabolism, hepatosplenomegaly, leukodystrophy, lipid histiocytosis (classical phosphatide), lipid storage disorder, lysosome storage disease, Niemann-Pick disease, neurodegeneration, neurological disorder, Neuronal Cholesterol Lipidosis, NPD, NPD type A, NPD type B, NPD type C, NPD type D, NPD type E, ophthalmoplegia, sphingolipidoses, sphingomyelin/cholesterol lipidosis.

types of the disease

Niemann-Pick disease (NPD) types A and B: NPD types A and B, also called type I, are both caused by a mutation in the SMPD1 gene. This gene carries instructions for cells to produce an enzyme called acid sphingomyelinase. This enzyme is found in the lysosomes, which are cellular compartments that digest and recycle materials within cells. Acid sphingomyelinase processes the lipid (fat) sphingomyelin. Mutations in the SMPD1 gene lead to a deficiency of acid sphingomyelinase, which results in the build up of sphingomyelin, cholesterol, and other lipids within cells and tissues of affected individuals.
People with NPD type A generally have less than 1% of normal acid sphingomyelinase production and usually die by 18 months of age. In contrast, individuals with NPD type B have about 10% of normal acid sphingomyelinase levels. Patients with NPD type B have fewer neurological problems and may survive into adulthood.
NPD types C and D: NPD types C and D are also called type II. Symptoms of NPD type C usually appear during childhood, although they sometimes occur during infancy and adulthood. NPD type C patients are not able to break down cholesterol and other lipids properly, causing excessive amounts of cholesterol to build up inside the liver and spleen. There is also an accumulation of other lipids in the brain.
Mutations in either NPC1 genes (95% of cases) or NPC2 genes (5% of cases) cause NPD type C. The NPC1 gene produces a protein that is located in membranes inside the cells and is involved in the movement of cholesterol and lipids within cell membranes. The NPC2 gene produces a protein that binds and transports cholesterol.
NPD type D is now considered a variant of NPD type C that originated in Nova Scotia.
NPD type E: An adult-onset form of NPD has been suggested and may be referred to as NPD type E.