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| {{Infobox_Disease |
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| Name = {{PAGENAME}} |
| | {{Niemann-Pick disease}} |
| Image = Niemann Pick disease micro.jpg|
| | '''For patient information click [[Niemann-Pick disease (patient information)|here]]''' |
| Caption = Bone marrow aspirate smear from a child with Niemann-Pick disease. A large foamy histiocyte typical of this disorder is illustrated. (Wright-Giemsa stain). <br> <small> [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology] </small> |
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| ICD10 = {{ICD10|E|75|2|e|70}} ([[ILDS]] E75.230) |
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| ICD9 = {{ICD9|272.7}} |
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| MeshID = D009542 |
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| {{Editor Help}} | | {{CMG}}; {{AE}} {{CH}} |
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| ==Overview==
| | {{SK}} NPD |
| '''Niemann-Pick disease''' is an [[autosomal recessive]] disorder affecting [[lipid]] metabolism (the breakdown and use of fats and [[cholesterol]] in the body), in a way which causes harmful amounts of lipids to accumulate in the [[spleen]], [[liver]], [[lungs]], [[bone marrow]], and [[brain]].
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| There are three variants of Niemann-Pick disease based on the [[genetics|genetic]] cause and the symptoms exhibited by the patient.
| | '''Type A Niemann-Pick disease''': classical Niemann-Pick disease; Niemann-Pick disease, acute neuronopathic form; sphingomyelin lipidosis; sphingomyelinase deficiency |
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| ==Genetics==
| | '''Type B Niemann-Pick disease''': Niemann-Pick disease, adult non-neuronopathic; Niemann-Pick disease, visceral; Niemann-Pick disease, type E |
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| Mutations in the [[NPC1]], [[NPC2]], and [[SMPD1]] [[gene]]s cause Niemann-Pick disease.
| | '''Type C Niemann-Pick disease''': Neurovisceral storage disease with vertical supranuclear ophthalmoplegia; Niemann-Pick disease with cholesterol esterification block; Niemann-Pick disease without sphingomyelinase deficiency; Niemann-Pick disease, chronic neuronopathic form; Niemann-Pick disease, subacute juvenile form; Niemann-Pick disease, type D; Nova Scotia Niemann-Pick disease |
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| This condition is inherited in an [[autosomal recessive]] pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the 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 for an affected child. [[Genetic counseling]] and [[genetic testing]] is recommended for families who may be carriers of Niemann-Pick.
| | ==[[Niemann-Pick disease overview|Overview]]== |
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| [[Image:autorecessive.svg|thumb|300px|left|Autosomal recessive inheritence]] | | ==[[Niemann-Pick disease historical perspective|Historical Perspective]]== |
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| ==Types== | | ==[[Niemann-Pick disease classification|Classification]]== |
| ===Types A and B===
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| 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.
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| 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 cell]]s 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 pathophysiology|Pathophysiology]]== |
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| 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.
| | ==[[Niemann-Pick disease causes|Causes]]== |
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| ===Type C=== | | ==[[Niemann-Pick disease differential diagnosis|Differentiating Niemann-Pick disease from other Diseases]]== |
| Type C is 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. 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.
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| Mutations in either the NPC1 or NPC2 gene cause Niemann-Pick disease, type C. The NPC1 gene produces a [[membrane protein|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 build up of lipids and cholesterol within cell membranes. The NPC2 gene produces a protein that binds and transports cholesterol, although its exact function is not fully understood.
| | ==[[Niemann-Pick disease epidemiology and demographics|Epidemiology and Demographics]]== |
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| ===Biochemical Transport=== | | ==[[Niemann-Pick disease risk factors|Risk Factors]]== |
| The molecular basis for this disease is extremely complex due to the role that [[endosome]] formation has on affected patients. Recently, three theories have attempted to explain the buildup of cholesterol in the lysosomes of affected patients of Niemann-Pick Disease Type C due to the malfunction of the protein NPC-1.
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| * The contention by Neufel et al is that the buildup of [[mannose 6-phosphate receptor]]s (MPRs) in the late endosome suggests that the retrograde breakdown of cholesterol via the Trans [[Golgi]] Network cannot occur.<ref name="npp">{{cite journal |author=Neufeld EB, Wastney M, Patel S, et al |title=The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo |journal=J. Biol. Chem. |volume=274 |issue=14 |pages=9627-9635 |year=1999 |pmid=10092649 |doi=}}</ref>
| | ==[[Niemann-Pick disease screening|Screening]]== |
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| * Another theory suggests that the blockage of retrograde cholesterol breakdown in the late endosome is due to decreased membrane elasticity and thus the return vesicles of cholesterol to the Trans [[Golgi]] Network cannot bud and form.
| | ==[[Niemann-Pick disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| The support of these theories has considerable evidence using mutant proteins [[in vitro]] to determine the buildup of [[cholesterol]] in the [[lysosomes]]. Researchers have also discovered that the NPC-1 protein may function as a pump of cholesterol.<ref name="tmp">{{cite journal |author=Davies JP, Chen FW, Ioannou YA |title=Transmembrane molecular pump activity of Niemann-Pick C1 protein |journal=Science |volume=290 |issue=5500 |pages=2295-2298 |year=2000 |pmid=11125140 |doi=10.1126/science.290.5500.2295}}</ref>
| | ==Diagnosis== |
| | [[Niemann-Pick disease history and symptoms| History and Symptoms]] | [[Niemann-Pick disease physical examination | Physical Examination]] | [[Niemann-Pick disease laboratory findings|Laboratory Findings]] | [[Niemann-Pick disease electrocardiogram|Electrocardiogram]] | [[Niemann-Pick disease x ray|X Ray]] | [[Niemann-Pick disease CT|CT]] | [[Niemann-Pick disease MRI|MRI]] | [[Niemann-Pick disease ultrasound|Ultrasound]] | [[Niemann-Pick disease other imaging findings|Other Imaging Findings]] | [[Niemann-Pick disease other diagnostic studies|Other Diagnostic Studies]] |
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| The overall effect of a malfunction in NPC-1 is that low levels or an absence of the protein lead to the abnormal accumulation of lipids and cholesterol in the cells of people with this condition.
| | ==Treatment== |
| | [[Niemann-Pick disease medical therapy|Medical Therapy]] | [[Niemann-Pick disease surgery|Surgery]] | [[Niemann-Pick disease primary prevention|Primary Prevention]] | [[Niemann-Pick disease secondary prevention|Secondary Prevention]] | [[Niemann-Pick disease cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Niemann-Pick disease future or investigational therapies|Future or Investigational Therapies]] |
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| == External links == | | ==Case Studies== |
| *[http://www.nnpdf.org/ National Niemann-Pick Disease Foundation]
| | [[Niemann-Pick disease case study one|Case #1]] |
| *[http://www.parseghian.org/ Ara Parseghian Medical Research Foundation]
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| *[http://www.niemannpick.org.uk/ Niemann-Pick Disease Group (UK)]
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| :''This article incorporates public domain text from [http://ghr.nlm.nih.gov The U.S. National Library of Medicine]''
| | ==Related Chapters== |
| | | * [[Lysosomal storage disease]] |
| ==References==
| | * [[Lipid storage disorders]] |
| {{reflist}}
| | * [[Gaucher's disease]] |
| | | * [[Tay-Sachs disease]] |
| {{Metabolic pathology}}
| | * [[Leukodystrophy]] |
| {{SIB}}
| | * [[Mucopolysaccharidoses]] |
| | * [[Hunter syndrome]] |
| | * [[Hurler disease]] |
| | * [[Mucolipidoses]] |
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| | [[Category:Endocrinology]] |
| [[Category:Neurology]] | | [[Category:Neurology]] |
| [[Category:Genetic disorders]]
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| [[Category:Autosomal recessive disorders]]
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| [[Category:Lysosomal storage diseases]]
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| [[de:Niemann-Pick-Krankheit]]
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| [[es:Enfermedad de Niemann-Pick]]
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| [[it:Malattia di Niemann-Pick]]
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| [[ru:Болезнь Ниманна — Пика]]
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| [[fi:Niemann–Pickin tauti]]
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| [[zh:尼曼匹克症]]
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