In 1914 albert niemann, a german pediatrician who primarily studied infant metabolism, published a description of an ashkenazi jewish infant with jaundice, nervous system and brain impairments, swollen lymph nodes lymphadenopathy, and an enlarged liver and spleen hepatosplenomegaly. Niemannpick disease is a rare genetic medical condition. Niemannpick type c npc is a lysosomal storage disease associated with mutations in npc1 and npc2 genes. Niemannpick disease is also called frontotemporal degeneration, and it is a kind of brain disease that causes dementia. Niemannpick disease npd is a group of inherited metabolic disorders in which harmful quantities of a fatty substance lipids accumulate in the spleen, liver, lungs, bone marrow, and brain. Symptoms may include lack of muscle coordination, brain degeneration, learning problems, loss of muscle tone, increased sensitivity to touch, spasticity, feeding and swallowing difficulties, slurred. Niemann pick disease type c npc is a rare progressive genetic disorder characterized by an inability of the body to transport cholesterol and other fatty substances lipids inside of cells. There have been recent developments in testing that make diagnosis easier and new therapies that aim to stabilise the disease process. Niemannpick c disease and mobilization of lysosomal cholesterol. In people with this condition, abnormal lipid metabolism causes harmful amounts of lipids to accumulate in the.
Niemannpick disease type c npc is an autosomal recessive neurometabolic disorder that rarely presents in adulthood, and is associated with cognitive decline, various movement disorders ataxia, chorea, dystonia, and myoclonus, a vertical. Niemannpick disease information page national institute. He reported that these anatomical disturbances resulted in the premature. A company limited by guarantee and registered in england and wales number 10646129.
Travis stork explains how niemannpick disease affects the body. Niemannpick disease npd is a lipid storage disorder that results from the deficiency of a lysosomal enzyme, acid sphingomyelinase. Niemannpick disease leads to the irregular and harmful accumulation of fatty substances within various tissues of the body, including liver, spleen, and brain tissue. Diagnosis of niemannpick diseasenational niemannpick. Niemannpick disease causes a variety of medical problems, and it often advances rapidly. Laboratory diagnosis of the niemannpick type c disease. Winsor and welch 1978 gave a full genetic discussion of the nova scotian or type d niemannpick disease. Niemann pick type c npc is a progressive and life limiting autosomal recessive disorder caused by mutations in either the npc1 or npc2 gene. Niemannpick disease originally was defined in terms of its histology as a reticuloendotheliosis. Previously, studies on niemannpick disease were performed on rodents with druginduced enzyme deficiencies, which was less than ideal.
The international niemannpick disease registry inpdr is a diseasespecific patient registry. There are four variants of this disease, categorized as type a, type b, type c, and type d. Niemannpick disease np refers to a group of inherited metabolic disorders known as lipid storage diseases. Df mice were cultured for 14 days in serumfree medium and then. Niemannpick disease is an inherited condition involving lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. Gene therapy may be effective method for treating niemannpick disease, type c1. Although npc differs in major respects from alzheimers. Niemannpick type c is an uncommon neurodegenerative lysosomal storage disorder that can cause a progressive neuropsychiatric syndrome associated with supranuclear vertical gaze palsy and a movement disorder. Niemannpick disease type c was found in 27% of infants initially diagnosed with inh and 8% of all infants evaluated for cholestasis. Depending in part on the age of onset, npc can present initially as a systemic disease, featuring prominent. Clinical trials are performed for experimental treatment with. Niemannpick disease type c npc is an autosomal recessive lipid lysosomal storage disorder. Niemannpick disease type c is an autosomal recessive disorder vanier and millat, 2003. They generally respond to standard treatment but refractory cases may occur.
Genetic and laboratory diagnostic approach in niemann pick. Niemannpick disease type c npc is difficult to diagnosis as the symptoms are nonspecific to the disease and will vary from person to person. Niemannpick disease alex gavlin and brad kligman niemannpick is an autosomal recessive genetic disorder resulting in abnormal lipid metabolism. Npc is also described as a neurovisceral disorder, as it affects visceral organs such as liver, spleen and lungs as well as the central and the peripheral nervous systems. Below are photos depicting the progression of niemannpick disease type c for two children in particular, as chronicled by their parents. One of these groups aims is to raise awareness among doctors of a disorder most have never heard of 1, so they can diagnose it sooner and put families in touch with support groups for help. Niemannpick disease is an inherited condition involving lipid metabolism. Niemannpick disease type c or niemannpick c disease, often abbreviated as npc or npc, is currently the generic name widely used to designate the condition, irrespective of which gene, npc1 or npc2, is mutated.
The original description of npd referred to what is currently termed npd type a, which is a fatal disorder of early childhood characterized by failure to thrive, hepatosplenomegaly, and a rapidly progressive ne. Niemannpick disease type c orphanet journal of rare. Isabel and toni now lead the niemannpick support groups in spain fundacion niemannpick and the uk niemannpick disease group respectively. Niemannpick disease is a lysosomal storage disorder that is characterized by failure to thrive and enlargement of the liver and spleen hepatosplenomegaly. Niemannpick type c npc disease is a lysosomal storage disease in which. The niemann pick syndrome arises from inherited defects that cause either a cellular accumulation of cholesterol, as in the type c form of niemann pick disease, or of sphingomyelin, in the case of niemann pick types a and b. These types are classified on the basis of genetic cause and the signs and symptoms of the condition. The progression of niemannpick diseasenational niemann. Niemannpick disease type c npc 1, 4, 5 npc is a lysosomal storage disease in which impaired intracellular lipid trafficking leads to excess storage of cholesterol and glycosphingolipids in the brain and other tissues.
It can result from a deficiency of the acid sphingomyelinase enzyme, leading to type a or b disease, or the npc1 or npc2 also called he1 proteins involved. For the first time, national institutes of health researchers have demonstrated in mice that gene therapy may be. Niemann pick disease type c nord national organization for. Enable javascript to view the expandcollapse boxes. Registered charity number england and wales 1175311. Niemannpick disease type a genetic and rare diseases. Pdf niemann pick disease a case report researchgate. In people with this condition, abnormal lipid metabolism causes harmful amounts of lipids to accumulate in the spleen, liver, lungs, bone marrow, and brain. Niemannpick disease is a condition that affects many body systems. An inherited disorder of lipid metabolism characterized by the accumulation of lipids in the spleen and.
Investigators at the national institute of neurological disorders and stroke ninds have identified two different genes that, when defective, contribute to niemann pick disease type c. This term now encompasses the historical niemannpick disease type d referring to the nova scotia isolate, later shown to be a genetic npc1 variant. Niemannpick disease npc is a rare advanced genetic cholesterol storage disorder. Npc is diagnosed by taking a small piece of skin a skin biopsy to see whether there is accumulation of fatty substances within the cells.
The progression of niemannpick disease is highly variable. Niemannpick disease type c npc is a rare progressive genetic disorder. Niemannpick disease npd, also called sphingomyelincholesterol lipidosis, is a group of autosomal recessive disorders associated with splenomegaly, variable neurologic deficits, and the storage of lipids including sphingomyelin and cholesterol. Read and know what niemannpick disease is as well as its causes, symptoms, diagnosis and treatment. Treatment of npc may require the coordinated efforts of a team of specialists. Niemann pick disease is an inherited condition involving lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. It is characterized by the bodys inability to transport cholesterol and other fatty substances lipids into the cells. Consensus clinical management guidelines for niemannpick. Niemannpick type c npc is a progressive and life limiting autosomal recessive disorder caused by mutations in either the npc1 or npc2 gene. Niemannpick type c npc is an inherited neurodegenerative disease of childhood and adolescence that develops from a failure of cholesterol trafficking within the endosomallysosomal pathway. Niemannpick disease type c npc is a hugely lifelimiting neurodegenerative disease caused by an accumulation of lipids fats in the liver, brain and spleen.
Niemannpick disease npd is an autosomal recessive disorder, observed most frequently in ashkenazi jews, where there is a deficiency of the lysosomal enzyme sphingomyelinase, leading to accumulation of sphingomyelin in cells of the monocytemacrophage system and reticular endothelial cells. Niemannpick disease is a rare hereditary condition that affects 1 in 15,000 people but can be extremely lifethreatening. Mutations in these genes are associated with abnormal endosomallysosomal trafficking, resulting in the accumulation of multiple tissue specific lipids in the lysosomes. Niemannpick disease type c in neonatal cholestasis at a. Niemann pick disease type c nord national organization.
Ninds scientists are studying the mechanisms by which lipids accumulating in these storage. Niemann pick disease market global industry analysis and. All types of niemannpick disease are autosomal recessive, which means that children with the disease have two copies of the abnormal gene. At least some types are characterized by foamy reticular cells containing phospholipids. Niemannpick type c disease npc is a genetically determined. Niemannpick disease type b is an allelic disorder characterized by visceral involvement only and survival into adulthood. Niemann pick is a rare, inherited disease that affects the bodys ability to metabolize fat cholesterol and lipids within cells. Niemann pick disease definition of niemann pick disease. Niemannpick disease type c npc is a devastating neurodegenerative disease caused by an accumulation of lipids fats in the liver, brain and spleen. Niemannpick disease is a group of genetic conditions, which affects the metabolism of fats or lipids in the body. Niemannpick disease information page what research is being done. This leads to the abnormal accumulation of these substances within various tissues of the body, including brain tissue. Patients with a retrospective diagnosis of niemannpick c disease have also. Niemannpick disease the embryo project encyclopedia.
Conclusion niemannpick disease type c should be considered in all infants with cholestasis, particularly those with splenomegaly or who are of hispanic descent. Niemann pick disease synonyms, niemann pick disease pronunciation, niemann pick disease translation, english dictionary definition of niemann pick disease. Niemannpick disease definition of niemannpick disease. At npuk we are dedicated to supporting the individuals and families affected by these conditions. These pages provide information about npd, its diagnosis and treatment, and the work that nnpdf is conducting to fund research and support families affected by niemannpick disease. This blood test identifies four mutations associated with niemannpick diseases, type a and b. Approximately 1 in 90 persons of ashkenazi jewish descent are carriers for niemannpick disease. Adult onset niemannpick disease type c presenting with. Pdf parkinsonism syndrome in heterozygotes for niemann. Pdf niemann pick disease npd is a rare autosomal re cessive metabolic disease characterized by lysosomal lipid storage. Kohlenhydratmodifizierte ernahrung bei niemannpick typ c. It is quite different from most other dementias, although a lot of people who are not experts, do not notice the difference. Lipids fatty materials such as waxes, fatty acids, oils, and cholesterol and proteins are usually broken down into smaller components to provide energy for the body.
Mayo clinic doctors are wellacquainted with this complicated disease and are experienced at distinguishing niemannpick from other diseases with similar symptoms. It has a wide range of symptoms that vary in severity. Niemannpick disease is an inherited disease that affects lipid metabolism, or the way fats, lipids, and cholesterol are stored in or removed from your body. Parkinsonism syndrome in heterozygotes for niemann pick c1 article pdf available in journal of the neurological sciences 33512 september 20 with 79 reads how we measure reads. Approximately 50% of cases present before 10 years of age, but manifestations may first be recognized as late as the sixth decade.
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