Niemann-Pick disease

March 22, 2017


Niemann-Pick disease

Natural Standard Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

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.


  • 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.

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.

Risk Factors

  • Parents that possess the gene for Niemann-Pick disease (NPD), even if they do not have the disease themselves, have a chance of passing the disease on to their children. Certain populations are known to have a higher incidence of people that carry the gene for NPD. The incidence of children born with NPD in the general population is 1 out of 150,000 people.

  • NPD types A and B occur more frequently among individuals of Ashkenazi (eastern and central European) Jewish decent. The incidence of children born with NPD within the Ashkenazi population is approximately 1 out of 40,000 people.

  • NPD type D was previously restricted to individuals of French-Acadian decent in Nova Scotia, where the incidence of children born with NPD type D is approximately 1 out of 100 people, until research showed that affected people have mutations associated with NPD type C1.

  • There is a higher-than-normal incidence of NPD type B in individuals from the Maghreb region, which is composed of Tunisia, Morocco, and Algeria.

  • There is a higher-than-normal incidence of NPD type C in the Spanish-American population of New Mexico and Colorado and among Puerto Ricans of Spanish decent.


  • General: Niemann-Pick disease (NPD) occurs when a person is born with a mutated, or abnormal, version of one of the following genes: NPC1, NPC2, or SMPD1. These genes provide instructions on how to make proteins that are essential for proper lipid (fat) processing. When lipids are processed improperly, toxic levels of lipids build up in the body and lead to organ failure.

  • Inheritance: NPD is an inherited disorder (meaning that is passed down among family members). Each gene has two variations, called alleles. One allele is inherited from each parent. NPD is inherited as an autosomal recessive disorder, which means that two mutated alleles (one from each parent) of a single gene must be inherited in order for a person to develop the disorder. Males and females are affected equally.

  • Most often, parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene. If both parents are carriers, there is a 25% chance with each pregnancy of having an affected child. Genetic counseling and genetic testing is recommended for families who may be carriers of NPD.

Signs and Symptoms

  • General: The symptoms and disease progression of all forms of Niemann-Pick disease (NPD) vary from person to person. Symptoms may develop at different times and progress at different rates. Because NPD is uncommon and symptoms vary widely, it is believed that many cases of NPD go undiagnosed.

  • NPD type A: Symptoms for NPD type A begin in the first few months of life and may include a lack of muscle coordination, brain degeneration, learning problems, loss of muscle tone, abdominal swelling, increased sensitivity to touch, spasticity (continuous muscle contraction), feeding and swallowing difficulties, irregular vocalization, hepatosplenomegaly (enlarged spleen), and enlarged liver. There may be a clouding of the transparent covering of the eye called the cornea. There may also be a characteristic cherry-red halo around the retina (the layer of cells along the back of the eyeball).

  • NPD type B: NPD type B symptoms are usually milder and occur late in childhood or adolescence. Abdominal swelling may be seen in early childhood, but there is almost no neurological involvement, such as loss of motor skills. Some patients may experience frequent respiratory infections. Other signs and symptoms may include bleeding, headaches, fatigue, digestive pain and problems, joint pain, and broken bones.

  • NPD type C: NPD type C usually affects school-aged children, but symptoms may occur anytime between infancy and adulthood. Symptoms may include movement difficulties, enlarged spleen and liver, jaundice, developmental delays, seizures, difficulty speaking, loss of muscle tone, tremors, vertical gaze palsy (trouble moving the eyes vertically), and coordination difficulties.

  • NPD type D: NPD type D symptoms are similar to NPD type C.

  • NPD type E: NPD type E occurs in adults and is not fully understood. Symptoms include swelling of the spleen and neurological problems.


  • General: Infants with Niemann-Pick disease (NPD) type A die during infancy. Patients with NPD types C and D often die during childhood. If symptoms of NPD develop later in life, the disease may be less severe and may lead to longer life spans, but it is rare for any person with NPD to reach 40 years of age. It is believed that the severity of NPD is related to the specific genetic alteration that caused the disease.

  • NPD types A and B: NPD types A and B are diagnosed by measuring the amount of acid sphingomyelinase in white blood cells. This test can be done using a blood or bone marrow sample. Such testing can tell if someone has NPD, but it cannot tell who carries the genetic mutation that causes the disease. DNA tests can be done to determine if an individual is a carrier of NPD. Prenatal testing may be done if there is a family history of NPD.

  • NPD types C and D: NPD types C and D are diagnosed by a skin biopsy. Biologists study how the skin cells from an individual grow and how they move and store cholesterol. DNA tests may also be done to check for alterations in the two genes (NPC1 and NPC2) that cause NPD type C. Higher-than-normal cholesterol levels can also be detected after taking a blood sample.

  • Additional tests for NPD include the slit-lamp eye exam (which provides a magnified, three-dimensional view of the different parts of the eye), liver biopsy, bone marrow testing, and sphingomyelinase enzyme tests.


  • Patients with Niemann-Pick disease (NPD) should regularly visit their doctor in order to treat and help prevent complications of NPD. Patients with NPD should avoid contact sports because of the risk of rupture of the spleen.

  • Patients with NPD type B are at an increased risk to develop liver failure and/or respiratory problems, which put stress on the heart and may ultimately lead to heart disease.

  • Removal of the spleen should be avoided, as it leads to rapid progression of lung disease.

  • Lung disease is progressive in patients with NPD type B and may result in supplemental oxygen being administered.

  • Other complications include blindness, brain damage with mental retardation and delayed development of physical skills, deafness, and death.


  • General: There is no cure or specific treatment for Niemann-Pick disease (NPD). Instead, treatment focuses on reducing the symptoms and delaying the onset of the disease if it is diagnosed early enough. A healthy, low-cholesterol diet is recommended, although research does not show that this diet slows the progression or cures NPD.

  • NPD type A: There is no known treatment for NPD type A. Most patients die before 18 months of age. Supportive treatment can be given to manage the symptoms of NPD type A. A multidisciplinary team including pulmonologists, cardiologists, liver and spleen specialists, nutritionists, physical therapists, and a gastroenterologist maybe needed.

  • NPD types B and C: Individuals with NPD types C and D are frequently placed on a low-cholesterol diet. However, this has not been proven to be clinically beneficial. Medications may be prescribed to control or relieve symptoms, such as seizures.

  • Bone marrow transplantation has been attempted in a few patients with NPD type B, with limited success due to complications. Clinical trials are ongoing for enzyme replacement therapy in adult patients with non-neurological NPD type B. Another promising treatment for late-onset NPD is to replace the mutant genes with healthy ones using gene therapy. The administration of neurosteroids, which are hormones found in the nervous system that are essential for proper brain function, also shows promise as a future treatment for NPD type B.

  • Canada has announced its approval of Zavesca® (miglustat) for the treatment of neurological symptoms of NPD type C, it is not a cure, but it has shown benefits in managing symptoms and slowing the progression of NPD type C.

Integrative Therapies

  • Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Niemann-Pick disease (NPD).


  • There is currently no known way to prevent Niemann-Pick disease (NPD).

  • If a person has a family history of NPD, genetic testing may be performed to determine if he or she carries mutant forms of the NPC1, NPC2, or SMPD1 genes. Although carriers do not have the disease, they can pass a copy of the mutated gene on to their children.

  • Prenatal DNA testing may be performed if there is a family history of NPD. However, there are health risks associated with prenatal testing, including miscarriage.

  • Before and after genetic testing, it is recommended that people meet with genetic counselors. These professionals can help patients understand the risks of having a child with NPD. A genetic counselor can also explain the different types of genetic tests, including their potential risks and benefits. These counselors can help patients understand and interpret their test results.

  • Patients diagnosed with NPD should undergo regular checkups with their doctors in order to reduce the risk of developing complications.

Author Information

  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).


Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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  2. Genetics Home Reference: A service of the U.S. National Library of Medicine. http://ghr.nlm.nih.gov.

  3. Maxfield FR, Tabas I. Role of cholesterol and lipid organization in disease. Nature. 2005 Dec 1;438(7068):612-21. View Abstract

  4. National Institute of Neurological Disorders and Stroke (NINDS). www.ninds.nih.gov.

  5. National Niemann-Pick Disease Foundation. www.nnpdf.org.

  6. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

  7. Schuchman EH. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis. 2007 Oct;30(5):654-63. View Abstract

  8. Sévin M, Lesca G, Baumann N, et al. The adult form of Niemann-Pick disease type C. Brain. 2007 Jan;130(Pt 1):120-33. View Abstract

  9. Vance JE. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett. 2006 Oct 9;580(23):5518-24. View Abstract

Copyright © 2013 Natural Standard (www.naturalstandard.com)

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.


March 22, 2017