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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

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.

Related Gene(s)

Changes in these genes are associated with Niemann-Pick disease.

  • NPC1
  • NPC2
  • SMPD1

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.

  • Baby's First Test (
  • Gene Review: Acid Sphingomyelinase Deficiency (
  • Gene Review: Niemann-Pick Disease Type C (
  • Genetic Testing Registry: Niemann-Pick disease, type A (
  • Genetic Testing Registry: Niemann-Pick disease, type B (
  • Genetic Testing Registry: Niemann-Pick disease type C1 (
  • Genetic Testing Registry: Niemann-Pick disease type C2 (
  • Genetic Testing Registry: Sphingomyelin/cholesterol lipidosis (
  • MedlinePlus Encyclopedia: Niemann-Pick (

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?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding Niemann-Pick disease?

autosomal ; autosomal recessive ; bone marrow ; breakdown ; cell ; cholesterol ; clotting ; deficiency ; developmental delay ; dystonia ; enzyme ; failure to thrive ; gene ; hepatosplenomegaly ; incidence ; inherited ; lipid ; metabolism ; muscle tone ; mutation ; nervous system ; neurological ; ophthalmoplegia ; phosphatide ; platelets ; population ; protein ; recessive ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (


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  • Guillemot N, Troadec C, de Villemeur TB, Clément A, Fauroux B. Lung disease in Niemann-Pick disease. Pediatr Pulmonol. 2007 Dec;42(12):1207-14. (
  • McGovern MM, Aron A, Brodie SE, Desnick RJ, Wasserstein MP. Natural history of Type A Niemann-Pick disease: possible endpoints for therapeutic trials. Neurology. 2006 Jan 24;66(2):228-32. (
  • Ory DS. The niemann-pick disease genes; regulators of cellular cholesterol homeostasis. Trends Cardiovasc Med. 2004 Feb;14(2):66-72. Review. (
  • Paul CA, Boegle AK, Maue RA. Before the loss: neuronal dysfunction in Niemann-Pick Type C disease. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):63-76. Review. (
  • Sévin M, Lesca G, Baumann N, Millat G, Lyon-Caen O, Vanier MT, Sedel F. The adult form of Niemann-Pick disease type C. Brain. 2007 Jan;130(Pt 1):120-33. Epub 2006 Sep 26. Review. (
  • Simonaro CM, Park JH, Eliyahu E, Shtraizent N, McGovern MM, Schuchman EH. Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient Niemann-Pick disease. Am J Hum Genet. 2006 May;78(5):865-70. Epub 2006 Mar 14. (
  • Sturley SL, Patterson MC, Balch W, Liscum L. The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):83-7. Review. (
  • Vance JE. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett. 2006 Oct 9;580(23):5518-24. Epub 2006 Jun 15. Review. (
  • Verot L, Chikh K, Freydière E, Honoré R, Vanier MT, Millat G. Niemann-Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2. Clin Genet. 2007 Apr;71(4):320-30. (
  • Walkley SU, Suzuki K. Consequences of NPC1 and NPC2 loss of function in mammalian neurons. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):48-62. Review. (
  • Wasserstein MP, Desnick RJ, Schuchman EH, Hossain S, Wallenstein S, Lamm C, McGovern MM. The natural history of type B Niemann-Pick disease: results from a 10-year longitudinal study. Pediatrics. 2004 Dec;114(6):e672-7. Epub 2004 Nov 15. (


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