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Niemann-Pick disease

Niemann-Pick disease

Reviewed January 2008

What is Niemann-Pick disease?

Niemann-Pick disease is an inherited condition involving lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. In people with this condition, abnormal lipid metabolism causes harmful amounts of lipids to accumulate in the spleen, liver, lungs, bone marrow, and brain.

This disorder is divided into four main types based on the genetic cause and the signs and symptoms. Niemann-Pick disease type A appears during infancy and is characterized by an enlarged liver and spleen (hepatosplenomegaly), failure to gain weight and grow at the expected rate (failure to thrive), and progressive deterioration of the nervous system. Due to the involvement of the nervous system, Niemann-Pick disease type A is also known as the neurological type. Children affected by this condition generally do not survive past early childhood.

Niemann-Pick disease type B has a range of features that may include hepatosplenomegaly, growth retardation, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as elevated levels of cholesterol and other lipids (fats), and decreased numbers of blood cells involved in clotting (platelets). Niemann-Pick disease type B is also known as the non-neurological type because the nervous system is not usually affected. People with Niemann-Pick disease type B usually survive into adulthood.

Niemann-Pick disease type C usually appears in childhood, although infant and adult onsets are possible. Signs of Niemann-Pick disease type C include severe liver disease, breathing difficulties, developmental delay, seizures, poor muscle tone (dystonia), lack of coordination, problems with feeding, and an inability to move the eyes vertically. People with this disorder can survive into adulthood. Niemann-Pick disease type C is further subdivided into types C1 and C2, each caused by a different gene mutation.

How common is Niemann-Pick disease?

Niemann-Pick disease type A occurs more frequently among individuals of Ashkenazi (eastern and central European) Jewish descent than in the general population. The incidence within the Ashkenazi population is approximately 1 in 40,000.

The incidence of both Niemann-Pick disease types A and B in all other populations is estimated to be 1 in 250,000.

The incidence of Niemann-Pick disease type C is estimated to be 1 in 150,000. The disease occurs more frequently in people of French-Acadian descent in Nova Scotia. The French-Acadians were previously designated as having Niemann-Pick disease type D. This term is no longer used since it was shown that affected people have mutations in the gene associated with Niemann-Pick disease type C1.

What genes are related to Niemann-Pick disease?

Mutations in the NPC1, NPC2, and SMPD1 genes cause Niemann-Pick disease.

Mutations in the SMPD1 gene cause Niemann-Pick disease types A and B. This gene provides instructions for producing an enzyme called acid sphingomyelinase. This enzyme is found in the lysosomes (compartments that digest and recycle materials in the cell), where it processes lipids such as sphingomyelin. Mutations in this gene lead to a deficiency of acid sphingomyelinase and the accumulation of sphingomyelin, cholesterol, and other kinds of lipids within the cells and tissues of affected individuals.

Mutations in either the NPC1 or NPC2 gene cause Niemann-Pick disease type C. The NPC1 gene provides instructions for producing a protein that is involved in the movement of cholesterol and lipids within cells. A deficiency of this protein leads to the abnormal storage of lipids within cells as seen in people with Niemann-Pick disease type C1. The NPC2 gene provides instructions to produce a protein that binds and transports cholesterol. Reduced or absent levels of this protein lead to the abnormal accumulation of lipids and cholesterol in the cells as seen in people with Niemann-Pick disease type C2. The exact functions of the NPC1 and NPC2 proteins are not fully understood.

Read more about the NPC1, NPC2, and SMPD1 genes.

How do people inherit Niemann-Pick disease?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Niemann-Pick disease?

These resources address the diagnosis or management of Niemann-Pick disease and may include treatment providers.

You might also find information on the diagnosis or management of Niemann-Pick disease in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about Niemann-Pick disease?

You may find the following resources about Niemann-Pick disease helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Niemann-Pick disease?

  • Classical Niemann-Pick Disease
  • DAF syndrome
  • lipoid histiocytosis (classical phosphatide)
  • Neuronal Cholesterol Lipidosis
  • NPD
  • Ophthalmoplegia, Supraoptic Vertical
  • Sphingomyelinase deficiency
  • Sphingomyelin/cholesterol lipidosis
  • Sphingomyelin lipidosis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about Niemann-Pick disease?

Where can I find general information about genetic conditions?

What glossary definitions help with understanding Niemann-Pick disease?

References (12 links)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

 
Reviewed: January 2008
Published: September 15, 2014