Niemann-Pick disease

What is Niemann-Pick disease?

Niemann-Pick disease is an inherited condition involving lipid metabolism (the breakdown and use of fats and cholesterol in the body) in which harmful amounts of lipids 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 exhibited by the patient. Type A Niemann-Pick disease begins during infancy and is characterized by an enlarged liver and spleen (hepatosplenomegaly), failure to thrive, and progressive deterioration of the nervous system. Children affected by this condition generally do not survive past early childhood. Type B disease may include signs of hepatosplenomegaly, growth retardation, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as abnormal cholesterol and lipid levels, and low numbers of blood cells involved in clotting (platelets). People affected by this type of Niemann-Pick disease usually survive into adulthood.

Niemann-Pick disease, type C is further subdivided into types C1 and C2, each caused by a different gene mutation. Both types C1 and C2 Niemann-Pick disease are most commonly characterized by onset in childhood, although infant and adult onsets are possible. Other signs include severe liver disease, breathing difficulties, developmental delay, seizures, increased 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.

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 people. The incidence for other populations is unknown.

Niemann-Pick disease, type B occurs in all populations; however, the incidence is unknown.

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

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 carries instructions for cells to produce 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 produces a protein that is located in membranes inside the cell and 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. The NPC2 gene produces a protein that binds and transports cholesterol, although its exact function is not fully understood. Extremely low levels or absence of this protein leads to the abnormal accumulation of lipids and cholesterol in the cells of people with this condition.

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. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Niemann-Pick Disease on Wikipedia

'''Niemann-Pick disease''' is an inherited condition involving lipid metabolism (the breakdown and use of fats and cholesterol in the body) in which harmful amounts of lipids accumulate in the spleen, liver, lungs, bone marrow, and There are four variants of Nieman-Pick disease based on the genetic cause and the symptoms exhibited by the patient. All variants are inherited in a autosomal recessive pattern. Type A Niemann-Pick disease begins during infancy and is characterized by an enlarged liver and spleen (hepatosplenomegaly), failure to thrive, and progressive deterioration of the nervous system. Children affected by this condition generally do not survive past early childhood. 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 people. The incidence for other populations is unknown. Type B disease may include signs of hepatosplenomegaly, growth retardation, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as abnormal cholesterol and lipid levels, and low numbers of blood cells involved in clotting (platelets). People affected by this type of Niemann-Pick disease usually survive into adulthood. Niemann-Pick disease, type B occurs in all populations. Niemann-Pick disease, type C is further subdivided into types C1 and C2, each caused by a different gene mutation. Both types C1 and C2 Niemann-Pick disease are most commonly characterized by onset in childhood, although infant and adult onsets are possible. Other signs include severe liver disease, breathing difficulties, developmental delay, seizures, increased muscle tone (dystonia), lack of coordination, problems with feeding, and ...   [ Read More ]

External Resources

Ara Parseghian Medical Research Foundation - About this foundation whose goal is to find a cure for the devastating Niemann-Pick Type C disease.

National Niemann-Pick Disease Foundation - Provides in depth education and support for patients and families. Also information about the foundation itself.

International Center for Types A and B Niemann-Pick Disease - Provides information on the prevention and treatment of this disorder for patients, physicians and scientists.

Niemann-Pick Disease - Information sheet on this disease including what it is, treatment, prognosis and research being done.

Elliott Lister - Niemann-Pick Type C Disease - Learn about the disorder, special needs equipment and find related sites.

Dana's Angels Research Trust - Information from this charitable organization on Niemann-Pick Type C disease and how individuals can contribute funds for research for this fatal childhood disease.

Lee King Benefit Buddy Tournament - Benefit event to raise research funds for the National Niemann-Pick Disease Foundation. Includes rules and pay-out details, past results, sponsorship information, and testimonials. [May not work in all browsers]

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