Variably protease-sensitive prionopathy: Difference between revisions

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{{Infobox medical condition (new)
{{DISPLAYTITLE:Variably Protease-Sensitive Prionopathy}}
| name           = Variably protease-sensitive prionopathy
{{Infobox medical condition
| synonyms       =  
| name         = Variably Protease-Sensitive Prionopathy
| image          = PMC3514380 1752-1947-6-348-1.png
| image       = <!-- Image of the condition, if available -->
| alt            =
| caption     = <!-- Caption for the image -->
| caption         = Protease senstitive and resistant prionopathies coexisting in this immunohistological test
| field       = [[Neurology]]
| pronounce      =  
| symptoms     = [[Dementia]], [[ataxia]], [[myoclonus]]
| field           =  
| onset       = Typically in the 60s
| symptoms       = [[Dementia]], behavioral and psychiatric symptoms, ataxia, parkinsonism
| duration     = Progressive
| complications  =
| causes       = [[Prion]]
| onset           = 70 years
| risks       = Genetic predisposition
| duration       =
| diagnosis    = [[Neuropathology]], [[Western blot]]
| types          =  
| treatment   = Supportive care
| causes         = [[Prion]]
| prognosis   = Poor
| risks           =  
| diagnosis       =
| differential   =  
| prevention      =
| treatment       =
| medication      =  
| prognosis       = Average survival 24 months
| frequency      =
| deaths          =  
}}
}}
'''Variably protease-sensitive prionopathy''' ('''VPSPr''') (formerly known as '''Protease Sensitive Prionopathy''') is a sporadic [[prion protein]] disease first described in an abstract for a conference on prions in 2006, and this study was published in a 2008 report on 11 cases. The study was conducted by Gambetti P., Zou W.Q., and coworkers from the United States National Prion Disease Pathology Surveillance Center.<ref name="pmid18571782">{{cite journal  |vauthors=Gambetti P, Dong Z, Yuan J, etal |title=A novel human disease with abnormal prion proteining sensitive to protease |journal=Ann. Neurol. |volume=63 |issue=6 |pages=697–708 |date=June 2008 |pmid=18571782 |doi=10.1002/ana.21420 |url= |pmc=2767200}}</ref><ref>{{cite web|title=The Merck Manual - Variably Protease-Sensitive Prionopathy (VPSPr)|url=http://www.merckmanuals.com/professional/neurologic_disorders/prion_diseases/variably_protease-sensitive_prionopathy_vpspr.html|publisher=Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.|accessdate=16 November 2014}}</ref> It was first identified as a distinct disease in 2010 by Zou W.Q. and coworkers from the United States National Prion Disease Pathology Surveillance Center.<ref>{{Cite journal| last1 = Zou | first1 = W.| last2 = Puoti | first2 = G.| last3 = Xiao | first3 = X.| last4 = Yuan | first4 = J.| last5 = Qing | first5 = L.| last6 = Cali | first6 = I.| last7 = Shimoji | first7 = M.| last8 = Langeveld | first8 = J.| last9 = Castellani | first9 = R.| last10 = Notari | first10 = S.| last11 = Crain | first11 = B.| last12 = Schmidt | first12 = R. E.| last13 = Geschwind | first13 = M.| last14 = Dearmond | first14 = S. J.| last15 = Cairns | first15 = N. J.| last16 = Dickson | first16 = D.| last17 = Honig | first17 = L.| last18 = Torres | first18 = J. M.| last19 = Mastrianni | first19 = J.| last20 = Capellari | first20 = S.| last21 = Giaccone | first21 = G.| last22 = Belay | first22 = E. D.| last23 = Schonberger | first23 = L. B.| last24 = Cohen | first24 = M.| last25 = Perry | first25 = G.| last26 = Kong | first26 = Q.| last27 = Parchi | first27 = P.| last28 = Tagliavini | first28 = F.| last29 = Gambetti | first29 = P.| title = Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein| journal = Annals of Neurology| volume = 68| issue = 2| pages = 162–172| year = 2010| pmid = 20695009| pmc = 3032610| doi = 10.1002/ana.22094}}</ref>


VPSPr is very rare, occurring in just 2 or 3 out of every 100 million people.<ref>{{Cite news|url=https://www.merckmanuals.com/professional/neurologic-disorders/prion-diseases/variably-protease-sensitive-prionopathy-vpspr|title=Variably Protease-Sensitive Prionopathy (VPSPr) - Neurologic Disorders - Merck Manuals Professional Edition|work=Merck Manuals Professional Edition|access-date=2018-03-04|language=en-US}}</ref> As of 2018, fourteen cases have been reported in the UK.<ref>{{Cite web|url=http://www.cjd.ed.ac.uk/sites/default/files/figs.pdf|title=Creutzfeldt - Jakob disease in the UK (By calendar year)|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=4 July 2018}}</ref> It has similarities to [[Creutzfeldt–Jakob disease]], but clinical manifestations differ somewhat, and the abnormal [[prion protein]] (PrP) is less resistant to digestion by proteases; some variants are more sensitive to proteases than others, hence the name: variably protease-sensitive.
'''Variably Protease-Sensitive Prionopathy''' (VPSPr) is a rare [[neurodegenerative disease]] classified as a [[prion disease]]. It was first described in 2008 and is characterized by its unique [[biochemical]] and [[neuropathological]] features. VPSPr is considered a sporadic prion disease, meaning it occurs without a known genetic mutation or infectious exposure.


Patients present with behavioral and psychiatric symptoms, speech deficits ([[aphasia]] and/or [[dysarthria]]) and progressive cognitive and motor decline ([[dementia]], [[ataxia]], [[parkinsonism]], [[psychosis]], [[aphasia]] and [[mood disorder]]). Average age at onset is 70 years, and duration of survival is 24 months. About 40% of patients have a family history of [[dementia]]. Like CJD, it can be mistaken for [[Alzheimer's dementia]].
==Epidemiology==
VPSPr is an extremely rare condition, with only a few dozen cases reported worldwide since its initial description. It typically affects individuals in their 60s, although cases have been reported in a range from the 40s to the 80s. There is no known [[gender]] predilection.


Diagnosis is difficult, as pathognomonic signs on MRI such as cortical ribboning or hockey stick sign, periodic sharp wave complexes on EEG, and tests for [[14-3-3 protein]] and [[tau protein]] are usually not helpful, and no mutations have been observed in the coding region of the PrP gene, unlike CJD and [[Variant CJD]].<ref name="pmid18570344">{{cite journal |vauthors=Will R, Head M |title=A new prionopathy |journal=Ann. Neurol. |volume=63 |issue=6 |pages=677–8 |date=June 2008 |pmid=18570344 |doi=10.1002/ana.21447 |url=}}</ref> The diagnosis can be made on [[pathology|pathological examination]]. There are unique microscopic and [[immunohistochemistry|immunohistochemical]] features, and the prions cannot be digested using proteases. Because 8 out of 10 patients had a positive family history of dementia in the original study, a genetic cause was suspected.
==Pathophysiology==
Some have suggested the disease may be a sporadic form of GSS.<ref>{{Cite journal | doi=10.3201/eid2501.180807| title=Variable Protease-Sensitive Prionopathy Transmission to Bank Voles| journal=Emerging Infectious Diseases| volume=25| pages=73–81| year=2019| last1=Nonno| first1=Romolo| last2=Notari| first2=Silvio| last3=Di Bari| first3=Michele Angelo| last4=Cali| first4=Ignazio| last5=Pirisinu| first5=Laura| last6=d'Agostino| first6=Claudia| last7=Cracco| first7=Laura| last8=Kofskey| first8=Diane| last9=Vanni| first9=Ilaria| last10=Lavrich| first10=Jody| last11=Parchi| first11=Piero| last12=Agrimi| first12=Umberto| last13=Gambetti| first13=Pierluigi| pmc=6302590}}</ref>
VPSPr is caused by the accumulation of an abnormal form of the [[prion protein]] (PrP). Unlike other prion diseases, the prion protein in VPSPr exhibits variable sensitivity to [[protease]] digestion, which is a key diagnostic feature. The exact mechanism by which the abnormal prion protein causes neurodegeneration is not fully understood, but it is believed to involve the conversion of normal cellular prion protein (PrP^C) into the disease-associated form (PrP^Sc), leading to [[neuronal loss]] and [[gliosis]].


==See also==
==Clinical Features==
* [[Creutzfeldt–Jakob disease]]
The clinical presentation of VPSPr is heterogeneous, but common symptoms include:
* [[Dementia]]: Progressive cognitive decline is a hallmark of the disease.
* [[Ataxia]]: Patients often exhibit unsteady gait and coordination difficulties.
* [[Myoclonus]]: Involuntary muscle jerks may be present.
 
Other symptoms can include [[visual disturbances]], [[aphasia]], and [[parkinsonism]]. The disease course is typically progressive, leading to severe disability and death within a few years of onset.
 
==Diagnosis==
Diagnosis of VPSPr is challenging and often requires a combination of clinical, biochemical, and neuropathological assessments. Key diagnostic tools include:
* [[Magnetic Resonance Imaging]] (MRI): May show cortical atrophy and other non-specific changes.
* [[Electroencephalogram]] (EEG): Typically does not show the periodic sharp wave complexes seen in [[Creutzfeldt-Jakob disease]].
* [[Cerebrospinal Fluid]] (CSF) analysis: Tests such as the 14-3-3 protein are often negative.
* [[Western Blot]]: Used to analyze the protease sensitivity of the prion protein, which is a distinguishing feature of VPSPr.
* [[Neuropathological examination]]: Post-mortem examination of brain tissue is definitive, revealing spongiform changes and PrP deposition.
 
==Treatment==
Currently, there is no cure for VPSPr. Treatment is supportive and focuses on managing symptoms. This may include:
* [[Pharmacological]] interventions for mood and behavioral symptoms.
* [[Physical therapy]] to assist with mobility and coordination.
* [[Occupational therapy]] to help maintain daily living skills.
 
==Prognosis==
The prognosis for VPSPr is poor, with most patients succumbing to the disease within 2 to 4 years after symptom onset. The variability in disease progression and symptomatology can make management challenging.
 
==Research Directions==
Ongoing research is focused on understanding the molecular mechanisms underlying VPSPr and developing potential therapeutic interventions. Studies are also exploring the genetic factors that may predispose individuals to this and other prion diseases.
 
==See Also==
* [[Prion disease]]
* [[Creutzfeldt-Jakob disease]]
* [[Gerstmann-Sträussler-Scheinker syndrome]]


==References==
==References==
{{Reflist}}
<references/>


== External links ==
==External Links==
{{Medical resources
* [Prion Alliance](https://www.prionalliance.org/)
|  ICD10          = A81.8
* [Centers for Disease Control and Prevention - Prion Diseases](https://www.cdc.gov/prions/index.html)
|  ICD9            = <!--{{ICD9|xxx}}-->
|  ICDO            =
|  OMIM            =
|  DiseasesDB      =
|  MedlinePlus    =
|  eMedicineSubj  =
|  eMedicineTopic  =
|  MeSH            =
|  GeneReviewsNBK  =
|  GeneReviewsName =
|  Orphanet        = 454742
}}
*{{Cite web|url=https://www.bbc.co.uk/news/health-10963132|title=Brain disease could affect more people, research finds|author=Caroline Parkinson|date=13 August 2010|publisher=BBC News}}


{{Prion diseases}}
{{Prion diseases}}
 
[[Category:Prion diseases]]
[[Category:Transmissible spongiform encephalopathies]]
[[Category:Neurological disorders]]
[[Category:Rare diseases]]
[[Category:Rare diseases]]
{{adapted}}
{{nervoussystem-disease-stub}}
{{stb}}

Revision as of 02:14, 2 January 2025


Variably Protease-Sensitive Prionopathy
Synonyms N/A
Pronounce N/A
Specialty N/A
Symptoms Dementia, ataxia, myoclonus
Complications N/A
Onset Typically in the 60s
Duration Progressive
Types N/A
Causes Prion
Risks Genetic predisposition
Diagnosis Neuropathology, Western blot
Differential diagnosis N/A
Prevention N/A
Treatment Supportive care
Medication N/A
Prognosis Poor
Frequency N/A
Deaths N/A


Variably Protease-Sensitive Prionopathy (VPSPr) is a rare neurodegenerative disease classified as a prion disease. It was first described in 2008 and is characterized by its unique biochemical and neuropathological features. VPSPr is considered a sporadic prion disease, meaning it occurs without a known genetic mutation or infectious exposure.

Epidemiology

VPSPr is an extremely rare condition, with only a few dozen cases reported worldwide since its initial description. It typically affects individuals in their 60s, although cases have been reported in a range from the 40s to the 80s. There is no known gender predilection.

Pathophysiology

VPSPr is caused by the accumulation of an abnormal form of the prion protein (PrP). Unlike other prion diseases, the prion protein in VPSPr exhibits variable sensitivity to protease digestion, which is a key diagnostic feature. The exact mechanism by which the abnormal prion protein causes neurodegeneration is not fully understood, but it is believed to involve the conversion of normal cellular prion protein (PrP^C) into the disease-associated form (PrP^Sc), leading to neuronal loss and gliosis.

Clinical Features

The clinical presentation of VPSPr is heterogeneous, but common symptoms include:

  • Dementia: Progressive cognitive decline is a hallmark of the disease.
  • Ataxia: Patients often exhibit unsteady gait and coordination difficulties.
  • Myoclonus: Involuntary muscle jerks may be present.

Other symptoms can include visual disturbances, aphasia, and parkinsonism. The disease course is typically progressive, leading to severe disability and death within a few years of onset.

Diagnosis

Diagnosis of VPSPr is challenging and often requires a combination of clinical, biochemical, and neuropathological assessments. Key diagnostic tools include:

Treatment

Currently, there is no cure for VPSPr. Treatment is supportive and focuses on managing symptoms. This may include:

Prognosis

The prognosis for VPSPr is poor, with most patients succumbing to the disease within 2 to 4 years after symptom onset. The variability in disease progression and symptomatology can make management challenging.

Research Directions

Ongoing research is focused on understanding the molecular mechanisms underlying VPSPr and developing potential therapeutic interventions. Studies are also exploring the genetic factors that may predispose individuals to this and other prion diseases.

See Also

References

<references/>

External Links


Prion diseases and transmissible spongiform encephalopathy
Prion diseases
in humans
Prion diseases
in other animals
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