Niemann–Pick disease: Difference between revisions
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All of these edits are made based on Dr. Marc Patterson o the Mayo Clinic's input -- he asked me to change this page to make it better. He is the leading neurologist on NPC |
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'''Niemann-Pick disease''' (pronounced nē′mahn pik) refers to a group of fatal inherited metabolic disorders |
'''Niemann-Pick disease''' (pronounced nē′mahn pik) refers to a group of fatal [[inherited metabolic disorders]] that are included in the larger family of [[lysosomal storage diseases]] (LSDs). Niemann Pick diseases are classified in a subgroup of LSDs called [[sphingolipidoses]] or [[lipid storage diseases]] in which harmful quantities of a fatty substances, called [[lipids]], accumulate in the [[spleen]], [[liver]], [[lungs]], [[bone marrow]], and [[brain]]. |
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Symptoms may be related to the organs in which they accumulate. Enlargement of the liver and spleen ([[heptosplenomegaly]]) may cause reduced appetite, abdominal distension and pain, and the enlarged spleen may trap platelets and other blood cells, leading to reduced numbers of these cell in the circulation. Storage in specific areas of the nervous system, causes specific symptoms. For example, storage in the [[cerebellum]] causes unsteady gait ([[ataxia]]), slurring of speech ([[dysarthria]]) and incoordinated swallowing ([[dysphagia]]). [[Basal ganglia]] dysfunction causes abnormal posturing of the limbs, trunk and face ([[dystonia]]) and upper brainstem disease causes impaired voluntary rapid eye movements (supranuclear gaze palsy) and sleep related disorders, including gelastic [[cataplexy]] (sudden loss of muscle tone associated with laughter), and sleep inversion (sleepiness during the day and wakefulness at night). More widespread disease involving the [[cerebral cortex]] and subcortical structures is responsible for gradual loss of intellectual abilities causing [[dementia]] and [[seizures]]. |
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⚫ | [[Albert Niemann]] published the first description of what is now known as Niemann-Pick disease, type A, in 1914 and [[Ludwig Pick]], a German neuropathologist, described the pathology of the disease in a series of papers in the 1930s.<ref>{{WhoNamedIt|synd|1029}}</ref><ref>A. Niemann. Ein unbekanntes Krankheitsbild. Jahrbuch für Kinderheilkunde, Berlin, N F, 1914. Volume 79: 1-10.</ref><ref>L. Pick. Der Morbus Gaucher und die ihm ähnlichen Krankheiten (die lipoidzellige Splenohepatomegalie Typus Niemann und die diabetische Lipoidzellenhypoplasie der Milz). |
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Ergebnisse der Inneren Medizin und Kinderheilkunde, Berlin, 1926, 29: 519-627.</ref> |
Ergebnisse der Inneren Medizin und Kinderheilkunde, Berlin, 1926, 29: 519-627.</ref> |
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[[Pick's disease]] is sometimes confused with Niemann-Pick disease but is a different disease, |
[[Pick's disease]] is sometimes confused with Niemann-Pick disease but is a different disease, one of the frontotemporal dementias, described by [[Arnold Pick]]. |
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==Genetics== |
==Genetics== |
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Mutations in the [[SMPD1]] [[gene]] cause Niemann-Pick disease types A and B, and mutations in [[NPC1]] and [[NPC2]] cause type C |
Mutations in the [[SMPD1]] [[gene]] cause Niemann-Pick disease types A and B, and mutations in [[NPC1]] and [[NPC2]] cause type C. Type D was originally separated from type C to delineate a group of otherwise identical patients who shared a common Nova Scotian ancestry. Patients in this group are now known to share a specific mutation in the NPC 1 gene, and NPC is now used to embrace both groups. The terms "Niemann-Pick type I" and "Niemann-Pick type II" were proposed to separate the high and low sphingomyelin forms of the disease in the early 1980s, before the molecular defects were described.<ref name="pmid9245994">{{cite journal |author=Greer WL, Riddell DC, Byers DM, ''et al'' |title=Linkage of Niemann-Pick disease type D to the same region of human chromosome 18 as Niemann-Pick disease type C |journal=American journal of human genetics |volume=61 |issue=1 |pages=139–42 |year=1997 |month=July |pmid=9245994 |pmc=1715879 |doi=10.1086/513899 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)64285-2}}</ref> |
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Niemann-Pick disease is inherited in an [[autosomal recessive]] pattern, which means |
Niemann-Pick disease is inherited in an [[autosomal recessive]] pattern, which means both copies, or [[alleles]], of the gene must be mutated (altered in such a way that function is impaired, in contrast to a polymorphism, in which the nucleotide sequence is altered but causes no functional disruption)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. |
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[[Image:autorecessive.svg|thumb|right|Autosomal recessive inheritence]] |
[[Image:autorecessive.svg|thumb|right|Autosomal recessive inheritence]] |
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In 1961, the following classification was introduced:<ref name="pmid13696518">{{cite journal |author=Crocker AC |title=The cerebral defect in Tay-Sachs disease and Niemann-Pick disease |journal=Journal of neurochemistry |volume=7 |issue= |pages=69–80 |year=1961 |month=April |pmid=13696518 |doi= |url=}}</ref><ref name="urlOMIM - NIEMANN-PICK DISEASE, TYPE C1; NPC1">{{cite web |url=http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=257220 |title=OMIM - NIEMANN-PICK DISEASE, TYPE C1; NPC1 |format= |work= |accessdate=2008-10-27}}</ref> |
In 1961, the following classification was introduced:<ref name="pmid13696518">{{cite journal |author=Crocker AC |title=The cerebral defect in Tay-Sachs disease and Niemann-Pick disease |journal=Journal of neurochemistry |volume=7 |issue= |pages=69–80 |year=1961 |month=April |pmid=13696518 |doi= |url=}}</ref><ref name="urlOMIM - NIEMANN-PICK DISEASE, TYPE C1; NPC1">{{cite web |url=http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=257220 |title=OMIM - NIEMANN-PICK DISEASE, TYPE C1; NPC1 |format= |work= |accessdate=2008-10-27}}</ref> |
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* A - classic infantile |
* type A - classic infantile |
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* B - visceral |
* type B - visceral |
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* C - subacute/juvenile |
* type C - subacute/juvenile |
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* D - Nova Scotian |
* type D - Nova Scotian |
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Now that the genetics are better understood, the condition can be classified as follows: |
Now that the genetics are better understood, the condition can be classified as follows: |
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*[http://www.nnpdf.ca// Niemann-Pick Disease Group Canada] |
*[http://www.nnpdf.ca// Niemann-Pick Disease Group Canada] |
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*[http://www.clinicaltrials.gov/ct/show/NCT00344331?order=1// National Institutes of Health Clinical Center Study On Niemann Pick Type C] |
*[http://www.clinicaltrials.gov/ct/show/NCT00344331?order=1// National Institutes of Health Clinical Center Study On Niemann Pick Type C] |
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*[http://podcasts.mayoclinic.org/2008/07/11/niemann-pick-disease-type-c/ |
*[http://podcasts.mayoclinic.org/2008/07/11/niemann-pick-disease-type-c/ Marc C. Patterson, MD, child neurologist at Mayo Clinic] |
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*[http://ccr.coriell.org/Sections/Collections/NIGMS/npc.aspx?PgId=247// Coriell Institute: Biobank that stores Niemann Pick Type C cells for research] |
*[http://ccr.coriell.org/Sections/Collections/NIGMS/npc.aspx?PgId=247// Coriell Institute: Biobank that stores Niemann Pick Type C cells for research] |
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*[http://www.addiandcassi.com/ Addi and Cassi Hempel: Identical twins living with Niemann Pick Type C disease] |
*[http://www.addiandcassi.com/ Addi and Cassi Hempel: Identical twins living with Niemann Pick Type C disease] |
Revision as of 20:19, 5 November 2008
Niemann–Pick disease | |
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Specialty | Endocrinology ![]() |
Niemann-Pick disease (pronounced nē′mahn pik) refers to a group of fatal inherited metabolic disorders that are included in the larger family of lysosomal storage diseases (LSDs). Niemann Pick diseases are classified in a subgroup of LSDs called sphingolipidoses or lipid storage diseases in which harmful quantities of a fatty substances, called lipids, accumulate in the spleen, liver, lungs, bone marrow, and brain.
Symptoms may be related to the organs in which they accumulate. Enlargement of the liver and spleen (heptosplenomegaly) may cause reduced appetite, abdominal distension and pain, and the enlarged spleen may trap platelets and other blood cells, leading to reduced numbers of these cell in the circulation. Storage in specific areas of the nervous system, causes specific symptoms. For example, storage in the cerebellum causes unsteady gait (ataxia), slurring of speech (dysarthria) and incoordinated swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs, trunk and face (dystonia) and upper brainstem disease causes impaired voluntary rapid eye movements (supranuclear gaze palsy) and sleep related disorders, including gelastic cataplexy (sudden loss of muscle tone associated with laughter), and sleep inversion (sleepiness during the day and wakefulness at night). More widespread disease involving the cerebral cortex and subcortical structures is responsible for gradual loss of intellectual abilities causing dementia and seizures.
Albert Niemann published the first description of what is now known as Niemann-Pick disease, type A, in 1914 and Ludwig Pick, a German neuropathologist, described the pathology of the disease in a series of papers in the 1930s.[1][2][3]
Pick's disease is sometimes confused with Niemann-Pick disease but is a different disease, one of the frontotemporal dementias, described by Arnold Pick.
Genetics
Mutations in the SMPD1 gene cause Niemann-Pick disease types A and B, and mutations in NPC1 and NPC2 cause type C. Type D was originally separated from type C to delineate a group of otherwise identical patients who shared a common Nova Scotian ancestry. Patients in this group are now known to share a specific mutation in the NPC 1 gene, and NPC is now used to embrace both groups. The terms "Niemann-Pick type I" and "Niemann-Pick type II" were proposed to separate the high and low sphingomyelin forms of the disease in the early 1980s, before the molecular defects were described.[4]
Niemann-Pick disease is inherited in an autosomal recessive pattern, which means both copies, or alleles, of the gene must be mutated (altered in such a way that function is impaired, in contrast to a polymorphism, in which the nucleotide sequence is altered but causes no functional disruption)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.
![](http://upload.wikimedia.org/wikipedia/commons/thumb/3/3e/Autorecessive.svg/220px-Autorecessive.svg.png)
Classification
In 1961, the following classification was introduced:[5][6]
- type A - classic infantile
- type B - visceral
- type C - subacute/juvenile
- type D - Nova Scotian
Now that the genetics are better understood, the condition can be classified as follows:
- Niemann-Pick disease, SMPD1-associated, which includes types A and B
- Niemann-Pick disease, type C, which includes types C1 and C2. (Type D is caused by the same gene as type C1.)
References
- ^ synd/1029 at Who Named It?
- ^ A. Niemann. Ein unbekanntes Krankheitsbild. Jahrbuch für Kinderheilkunde, Berlin, N F, 1914. Volume 79: 1-10.
- ^ L. Pick. Der Morbus Gaucher und die ihm ähnlichen Krankheiten (die lipoidzellige Splenohepatomegalie Typus Niemann und die diabetische Lipoidzellenhypoplasie der Milz). Ergebnisse der Inneren Medizin und Kinderheilkunde, Berlin, 1926, 29: 519-627.
- ^ Greer WL, Riddell DC, Byers DM; et al. (1997). "Linkage of Niemann-Pick disease type D to the same region of human chromosome 18 as Niemann-Pick disease type C". American journal of human genetics. 61 (1): 139–42. doi:10.1086/513899. PMC 1715879. PMID 9245994.
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Crocker AC (1961). "The cerebral defect in Tay-Sachs disease and Niemann-Pick disease". Journal of neurochemistry. 7: 69–80. PMID 13696518.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ "OMIM - NIEMANN-PICK DISEASE, TYPE C1; NPC1". Retrieved 2008-10-27.
External links
- National Niemann-Pick Disease Foundation (USA)
- Ara Parseghian Medical Research Foundation
- Niemann-Pick Disease Group (UK)
- Niemann-Pick Disease Group Canada
- National Institutes of Health Clinical Center Study On Niemann Pick Type C
- Marc C. Patterson, MD, child neurologist at Mayo Clinic
- Coriell Institute: Biobank that stores Niemann Pick Type C cells for research
- Addi and Cassi Hempel: Identical twins living with Niemann Pick Type C disease
- Testing labs for Niemann Pick Type C
- Clinical Description of Niemann Pick Type C
- Genetics Home Reference on Niemann Pick Disease
- Hide and Seek Foundation for Lysosomal Storage Diseases
- This article incorporates public domain text from The U.S. National Library of Medicine