Risk Factors (Genetics & Inherited Conditions)
Individuals who have family members with Niemann-Pick disease are at risk for the condition. Other individuals at risk are those of Ashkenazi Jewish heritage, who have an increased chance of having types A and B. People of Nova Scotian and French Canadian ancestry are at risk for type C, as is the Spanish American population of southern New Mexico and Colorado. Individuals of North African ancestry, who come from the Maghreb region, including Tunisia, Morocco, and Algeria, are at risk for type B.
(The entire section is 83 words.)
Etiology and Genetics (Genetics & Inherited Conditions)
Niemann-Pick disease types A and B result from mutations in the SMPD1 gene, which is found on the short arm of chromosome 11 at position 11p15.4-p15.1. This gene encodes a protein known as sphingomyelin phosphodiesterase 1, acid lysosomal, or more simply acid sphingomyelinase. Found in the lysosomes (cellular organelles that digest and recycle molecules), this enzyme catalyzes the conversion of sphingomyelin into ceramide (two different lipid molecules). This lipid conversion is essential for normal cell function, since its absence results in the accumulation of sphingomyelin, cholesterol, and other lipids to toxic levels. Those gene mutations that result in a totally inactive enzyme generally cause the more severe form of the disease, type A, whereas mutations that allow the altered protein to retain some small fraction of normal activity are generally associated with the milder type B disease.
Inheritance of Niemann-Pick disease types A and B is quite unusual and follows a pattern known as genomic imprinting. Only the gene inherited from the mother is active; the paternal copy is permanently inactivated. Therefore the child will be healthy or affected depending upon whether the maternal gene copy is normal or mutated.
Type C1 disease is caused by mutations in the NPC1 gene (at position 18q11-q12), while type C2 disease results from mutations in the NPC2 gene, located on the long arm...
(The entire section is 380 words.)
Symptoms (Genetics & Inherited Conditions)
Symptoms of Niemann-Pick disease may develop during infancy, childhood, or the teen years, depending on the type of the disease. Symptoms vary. Not all patients will develop every symptom. Symptoms usually worsen over time.
Symptoms of type A begin within the first few months of life. They may include yellow skin and eye coloration, an enlarged belly (due to enlarged liver and spleen), mental retardation, loss of motor skills, difficulty swallowing and feeding, failure to thrive, seizures, visual problems, spastic movements (later in the disease), and rigid muscles (later in the disease).
Type B symptoms start during the preteen years. They may include yellow skin and eye coloration, an enlarged belly (due to enlarged liver and spleen), enlarged lymph nodes, osteoporosis or brittle bones, breathing difficulties, and frequent respiratory infections.
Symptoms of types C may start in infancy, childhood, or the teen years. They may include yellow skin and eye coloration, an unsteady gait, trouble walking, difficulty swallowing, the inability to look up or down, vision loss, hearing loss, and slurred speech. Other symptoms may include enlarged spleen and liver, loss of motor skills, difficulty swallowing, learning problems, a sudden loss of muscle tone, tremors, seizures, and psychosis or dementia.
(The entire section is 200 words.)
Screening and Diagnosis (Genetics & Inherited Conditions)
The doctor will ask about a child’s symptoms and medical history and will perform a physical exam. Tests for all types of Niemann-Pick disease may include a complete blood cell count (CBC), the measurement of acid sphingomyelinase activity in white blood cells, and deoxyribonucleic acid (DNA) testing to look for a mutated gene associated with the disease.
A skin biopsy, the removal of a skin sample to check how it transports and stores cholesterol, may be used to test for type C.
(The entire section is 83 words.)
Treatment and Therapy (Genetics & Inherited Conditions)
No specific or effective treatment currently exists for Niemann-Pick disease. Patients with type B may be given oxygen to help with lung problems. Research is focusing on the use of bone marrow transplantation, enzyme replacement therapy, and gene therapy.
(The entire section is 39 words.)
Prevention and Outcomes (Genetics & Inherited Conditions)
There are no specific guidelines for preventing Niemann-Pick disease. Prevention measures are currently available in the areas of genetic testing and prenatal diagnosis. Individuals who have Niemann-Pick disease or have a family history of the disorder can talk to a genetic counselor when deciding to have children.
(The entire section is 47 words.)
Further Reading (Genetics & Inherited Conditions)
EBSCO Publishing. Health Library: Niemann-Pick Disease. Ipswich, Mass.: Author, 2009. Available through http://www.ebscohost.com.
Fauci, Anthony S., et al., eds. Harrison’s Principles of Internal Medicine. 17th ed. New York: McGraw-Hill Medical, 2008.
Goldman, Lee, and Dennis Ausiello, eds. Cecil Medicine. 23d ed. Philadelphia: Saunders Elsevier, 2008.
Kleigman, Robert M., et al., eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia: Saunders Elsevier, 2007.
Kumar, Vinay, Abul K. Abbas, and Nelson Fausto, eds. Robbins and Cotran Pathologic Basis of Disease. 7th ed. St. Louis: MD Consult, 2004.
(The entire section is 83 words.)
Web Sites of Interest (Genetics & Inherited Conditions)
Canadian Chapter of the National Niemann-Pick Disease Foundation. http://www.nnpdf.ca
Genetics Home Reference. http://ghr.nlm.nih.gov
Health Canada. http://www.hc-sc.gc.ca/index-eng.php
National Institute of Neurological Disorders and Stroke: NINDS Niemann-Pick Disease Information Page. http://www.ninds.nih.gov/disorders/niemann/niemann.htm
National Niemann-Pick Disease Foundation. http://www.nnpdf.org
(The entire section is 58 words.)
Causes and Symptoms (Magill’s Medical Guide, Sixth Edition)
Niemann-Pick disease (NPD), which consists of several lipid storage diseases, is characterized by an enlarged liver and spleen and the accumulation of fatlike sphingomyelin and cholesterol. Many patients have enlarged spleens and livers soon after birth and develop severe mental damage. In others, symptoms lag; mental damage may not occur, or organ enlargement and mental damage may be postponed. The main forms, types A through C, are attributable to low levels of sphingomyelinase, which normally alters sphingomyelin for use and excretion.
Type A, or infantile NPD, is the most common type. The abdominal organs enlarge, and nervous system damage occurs in early infancy. The spleen and liver enlarge by the age of six months, motor function and intellectual capabilities are then lost, and death occurs by four years of age. Patients are emaciated, jaundiced, and have swollen abdomens and cherry-red spots in the macular region of the eye. Large histiocytes (foam cells) abound in the bone marrow, spleen, lymph nodes, adrenal glands, and lungs.
Type B, or juvenile nonneuropathic NPD, is also common. Enlarged abdominal organs develop as quickly as in type A, but no neurological impairment occurs. An enlarged spleen appears first, followed by liver enlargement. Lungs are often so damaged that frequent breathlessness occurs. Abdominal pain is caused by the huge size of the liver, and the patient is susceptible to respiratory...
(The entire section is 589 words.)
Treatment and Therapy (Magill’s Medical Guide, Sixth Edition)
Niemann-Pick disease can be prevented only through the enzymatic and genetic testing of prospective parents. Members of at-risk ethnic groups can be tested for sphingomyelinase in their lymphocytes and muscle cells. Genetic counseling can also be used. The disease is transmitted through an autosomal recessive gene, so both parents must carry the gene to transmit disease. If both parents are carriers of a defective NPD gene, each of their children has a 25 percent chance of having the disease and a 50 percent chance of being an asymptomatic carrier.
There is no cure for Niemann-Pick disease. Therapeutic approaches include spleen removal, which diminishes abdominal pain, but it is not widely used. Patients with lung damage who experience frequent respiratory infections and pneumonia are treated with antibiotics, but long courses and high doses are required. Bone marrow transplantation has been done, with mildly encouraging results, but it is not a common treatment. Some children or teenagers with type C disease have been helped by low-cholesterol diets. However, the life expectancy of patients with NPD has not been prolonged much.
(The entire section is 176 words.)
Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
In 1914, Albert Niemann, a German pediatrician, reported an eighteen-month-old Jewish child with huge liver and spleen, swollen lymph glands, and jaundice. The child had poor motor control, could not suckle, and died before age two. Postmortem examination showed large lipid deposits in the liver, spleen, lymph nodes, kidneys, and adrenal glands. The overall symptoms and rapid death suggested a new illness. In the 1920’s, Ludwig Pick studied other cases and named Niemann-Pick disease. NPD, seen in all ethnic groups, is most common in Ashkenazic Jews. Type B patients are often of Spanish ancestry. Type C, which is less common, occurs most in Nova Scotians.
It is believed that enzyme replacement therapy (mostly sphingomyelinase) may ease the lives of NPD victims when an effective methodology for the frequent delivery of purified enzymes is developed and the enzymes are available in sufficient amounts. Recombinant deoxyribonucleic acid (DNA) research should contribute greatly. However, such treatment of severe NPD (types A and C) will be difficult because of the need to deliver enzymes to the brain.
Another avenue is transplanting healthy livers and spleens, which is presently done to treat other diseases. The problems are scarce donated organs and difficulty placing them in debilitated NPD patients. Transplantation may prove more promising in the future. Also, researchers have identified animal models and...
(The entire section is 232 words.)
For Further Information: (Magill’s Medical Guide, Sixth Edition)
Lichtman, Marshall A., et al., eds. Williams Hematology. 7th ed. New York: McGraw-Hill, 2006. Contains information on foam cells and Niemann-Pick disease. Includes illustrations, references, and an index.
National Institute of Neurological Disorders and Strokes. “Niemann-Pick Disease Information Page.” http://www.ninds.nih.gov/disorders/niemann. A U.S. government Web site devoted to this disease.
National Niemann-Pick Disease Foundation. http://www.nnpdf.org. A group that promotes advocacy, research, support, and awareness.
Parker, James, and Phillip Parker, eds. Official Parent’s Sourcebook on Niemann-Pick Disease: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. Useful in helping laypersons understand the scientific concepts associated with Niemann-Pick disease. Includes good references for research foundations and support groups.
Raddidadi, Ali A., and Abdulazix Al Twaim. “Type A-Niemann-Pick Disease.” Journal of European Academy of Dermatology and Veneriology 14 (July, 2000): 301-303. A case study showing the disease course. Good illustrations and references.
(The entire section is 151 words.)
Niemann-Pick disease (Encyclopedia of Genetic Disorders)
Niemann-Pick disease (NPD) is a disorder of fat metabolism that causes abnormalities of the skin, eyes, musculoskeletal system, nervous system, liver, and lymphoid organs. It is named for German pediatricians Albert Niemann (1880-1921) and Ludwig Pick (1898-1935). Six types of the disease have been identified (A, B, C, D, E, and F).
Niemann-Pick disease is inherited through an autosomal recessive trait. The different types of NPD are characterized by an abnormal accumulation of sphingomyelin. A sphingomyelin is any group of sphingolipids (consists of a lipid and a sphingosine) containing phosphorus. It occurs primarily in the tissue of the nervous system.
Some characteristics of Niemann-Pick disease may be common for all types. Common symptoms include jaundice, hepatosplenomegaly (enlargement of the liver and spleen), physical and mental impairment, and feeding difficulties. Symptoms for most types of NPD (A, B, C, and D) are seen in infancy or early childhood.
Alternate names associated with the NPD disorder are lipid histiocytosis, sphingomyelin lipidosis, and sphingomyelinase deficiency.
(The entire section is 1988 words.)
Niemann-Pick Disease (Encyclopedia of Neurological Disorders)
Niemann-Pick disease (NPD) is a term that defines a group of diseases that affect metabolism and which are caused by specific genetic mutations. Currently, there are three categories of Niemann-Pick diseases: type A (NPD A), the acute infantile form; type B (NPD-B), a less common, chronic, non-neurological form; and type C (NPD-C), a biochemically and genetically distinct form of the disease.
NPD-A is a debilitating neurodegenerative (progressive nervous system dysfunction) childhood disorder characterized by failure to thrive, enlarged liver, and progressive neurological deterioration, which generally leads to death by three years of age. In contrast, NPD-B patients have an enlarged liver, no neurological involvement, and often survive into adulthood. NPD-C, although similar in name to types A and B, is very different at the biochemical and genetic level. People with NPD-C are not able to metabolize cholesterol and other lipids properly within the cells. Consequently, excessive amounts of cholesterol accumulate in the liver and spleen. The vast majority of children with NPD-C die before age 20, and many before the age of 10. Later onset of symptoms usually leads to a longer life span, although death usually occurs by age forty.
(The entire section is 1355 words.)