Citlali Rodriguez
7/19/15
Prions: Symptoms and Incubation Periods
Prions are the cause of awful degenerative diseases that cause their patients to undergo
sufferable symptoms. Symptoms often include dementia, loss of coordination, and
muscle spasms. These diseases are fatal without treatment and result in painful deaths.
These diseases are not extremely contagious. They need specific conditions to infect
others. Infection usually occurs through direct contact of infected tissue, genetics, or
mutations. These diseases are not a risk for epidemics. Many of these diseases have the
same symptoms but certain diseases have symptoms that are very specific to them which
distinguishes them from each other.
This research paper is going to be about four different human diseases and their
symptoms caused by a mutated prion protein. Prions are responsible for a number of
degenerative brain diseases in humans. Diseases such as Kuru, Gerstmann-Straussler-Scheinker,
Fatal Familial Insomnia, and many forms of Creutzfeldt - Jakob Disease are caused by this fatal
protein and often leads to many similar symptoms as well as symptoms specific for each disease.
Another curious fact about each of these diseases is that their incubation periods could range
from a couple months to several decades. It is important for a physician to identify symptoms
and be able to differentiate between each disease because the progression of each disease is
different.
Kuru: Incubation Period
Kuru, for example, is most common in Africa and causes it’s victims to develop impaired
movement and sometimes even a “grotesque laughter” (Hornlimann, Riesner, and Kretzschmar,
188). This disease is acquired from one of two ways of either ingestion of various amounts of
infected brains of the deceased or through parenteral transmission, which is acquiring the disease
through contamination of cuts (Hornlimann, Riesner, and Kretzschmar, 187). There is a higher
chance of contracting the disease when it’s through parenteral transmission. Parenteral
transmission also has a shorter incubation period than oral transmission even if the patient
encountered the same amount of infective tissue (Hornlimann, Riesner, and Kretzschmar, 187) .
The incubation period ranges from 4 years to several decades (Hornlimann, Riesner, and
Kretzschmar, 187).
Kuru: Symptoms
The initial phase of the disease begins with headaches and impaired movement caused by
joint and limb pain (Hornlimann, Riesner, and Kretzschmar, 188). The patient also begins to
experience euphoria and this phase of the disease gave Kuru the popular name of the “laughing
death” due to the terrible laughter patients began to experience at an early stage of the disease
(Hornlimann, Riesner, and Kretzschmar, 188). For obvious reasons this symptom disappeared at
the terminal stage of the disease (Hornlimann, Riesner, and Kretzschmar, 188).
About a month after the initial symptoms unsteadiness in gait and clumsiness became
apparent in patients (Hornlimann, Riesner, and Kretzschmar, 188). As the disease progressed a
“rough rhythmical shaking” of the patient’s entire body developed, especially when standing up
(Hornlimann, Riesner, and Kretzschmar, 188). It began to be commonly called the “Kuru
tremor” by the villagers (Hornlimann, Riesner, and Kretzschmar, 188). Several months after the
initial symptoms of Kuru other symptoms such as dysmetria, an inability to function properly
due to a faulty judgement of distance, dysarthria, stuttering caused by a nerve defect, and
hypotonia, decreased muscle tone begin to take hold of the patient (Hornlimann, Riesner, and
Kretzschmar, 188).
During the intermediate stage of the disease intermittent strabismus develops which
causes intersperse problems of vision where both eyes could no longer be directed at the same
object at the same time (Hornlimann, Riesner, and Kretzschmar, 188). Progression of the disease
was also identified by cerebellar ataxia which are lesions of the cerebellum and cause the
inability to coordinate balance (Hornlimann, Riesner, and Kretzschmar, 188).
During the terminal stages of this disease patients begin to start losing control of all
motor coordination and begin experiencing dementia (Hornlimann, Riesner, and Kretzschmar,
188). Risk factors mainly consisted of ingestion of infected tissue which provided means of
transmission (Hornlimann, Riesner, and Kretzschmar, 191). The epidemic could only be
sustained while “endocannibalistic mortuary practices” we’re still in use because it provides the
necessary amount of “intraspecies recycling” (Hornlimann, Riesner, and Kretzschmar, 191).
Gerstmann-Straussler-Scheinker: Symptoms and Incubation Period
Gerstmann-Straussler-Scheinker (GSS) is a familial or genetic prion disease “with an
autosomal dominant mode of inheritance” that is associated with a mutation in codon 102 of
PRNP (Hornlimann, Riesner, and Kretzschmar, 212). For the reason that it is a genetic disease, it
could not be acquired so there is no natural incubation period that could be properly observed
(Hornlimann, Riesner, and Kretzschmar, 211). To accommodate, scientists infected mice and rats
with GSS and observed an incubation period from 20-32 weeks (Hornlimann, Riesner, and
Kretzschmar, 212). The average age of onset symptoms is from the late 30’s to the mid 60’s
(Morrison, 270). Patients experience severe symptoms such as progressive spinal ataxia which is
a fatal neurodegenerative disorder (Hornlimann, Riesner, and Kretzschmar, 212). Initial
symptoms of the disease include a gradual loss of short-term memory and progressive gait ataxia
(loss of coordination) when the patient is under stress (Morrison, 270). During later stages of the
disease patients experience forgetfulness, rigidity, bradykinesia (slow movements), reduced
intellectual performance, and severe dementia (Morrison, 270). Psychotic depression has also
been witnessed (Morrison, 270). Without treatment rapid weight loss and death usually occur
within a year of the onset of Parkinsonian symptoms (Morrison, 270). About 80% of GSS
patients end up having dementia (Hornlimann, Riesner, and Kretzschmar, 212). The duration of
the illness is longer than 5 years in 31% of cases while the median is 39 months (Hornlimann,
Riesner, and Kretzschmar, 212). The only risk factor of contracting GSS are genetic factors
(Hornlimann, Riesner, and Kretzschmar, 213). While GSS is very closely related to CJD it is
important to examine PRNP and use immunoblotting to distinguish the two (Hornlimann,
Riesner, and Kretzschmar, 213).
Fatal Familial Insomnia
Fatal Familial Insomnia (FFI) is a very uncommon disease that was discovered in 1986
(Hornlimann, Riesner, and Kretzschmar, 216). It is a neurodegenerative disorder. Similarly to
GSS, it is not acquired so scientists had to observe the incubation period through transmission of
the disease to mice. Interestingly males are affected more with FFI (Hornlimann, Riesner, and
Kretzschmar, 217).
Fatal Familial Insomnia: heterozygous or homozygous
A tell-tale characteristic of this disease is a disturbance in sleep cycles (insomnia) and
other progressive neurological deficiencies (Hornlimann, Riesner, and Kretzschmar, 217).
Cognitive decline was also observed in 78% of FFI patients (Hornlimann, 217). PET scans of
patients usually reveal hypometabolism in the thalamus and mild hypometabolism in the cortex
which decreases in body temperature, consequently slowing down all enzymatic reactions
(Hornlimann, Riesner, and Kretzschmar, 217). The progression of FFI depends on whether or
not the patient was homozygous or heterozygous for the MET gene at PRNP codon 129
(Hornlimann, Riesner, and Kretzschmar, 217). If the patient is homozygous there will be rapid
progression; whereas if the patient is heterozygous there will be slow progression of the disease
(Hornlimann, Riesner, and Kretzschmar, 217).
Fatal Familial Insomnia: Symptoms
During the initial phase of the disease, homozygous patients experienced symptoms such
as dream-like episodes, insomnia, and dysautonomy, problems with the nerves that carry
information from the brain and spinal cord to most of the body (Hornlimann, Riesner, and
Kretzschmar, 217). Heterozygous patients on the other hand experienced completely different
symptoms. They suffered from ataxia, the loss of full control of bodily fluids, dysarthria
(stammering), sphincter dysfunction, and grand-mal attacks which are a loss of consciousness
and violent muscle contractions (Hornlimann, Riesner, and Kretzschmar, 217). Patients also
often had severe damage to the cortex of their brain (Hornlimann, Riesner, and Kretzschmar,
217). During the terminal stage of this disease patients developed stupor, a state of insensitivity
and coma (Morrison, 300). The only risk factor of this disease is a mutation of PRNP
(Hornlimann, Riesner, and Kretzschmar, 220).
Creutzfeldt-Jakob Disease
Creutzfeldt-Jakob Disease (CJD) is another progressive neurological disease caused by
prions. There are many different forms of CJD which include sporadic CJD, familial/genetic
CJD, and other forms that are acquired (Hornlimann, Riesner, and Kretzschmar, 195). Sporadic
CDJ (sCJD) makes up the majority of CJD cases and usually is caused by a spontaneous change
of PrP which begins a chain reaction and ultimately ends up making an infectious prion
(Hornlimann, Riesner, and Kretzschmar, 196). On the other hand, Familial CJD (fCJD) is passed
down through genes and has been identified as an autosomal dominant mode of inheritance.
(Hornlimann, Riesner, and Kretzschmar, 196). There are two forms of CJD that are acquired,
Iatrogenic (iCJD) and Variant (vCJD) (Hornlimann, 196). ICJD is caused by medical accidents
such as through contaminated growth hormone preparations from the pituitary gland of deceased
people (Hornlimann, Riesner, and Kretzschmar, 196). Or for example, contaminated grafts of the
dura mater and neurosurgery that includes corneal transplantations (Hornlimann, Riesner, and
Kretzschmar, 196). VCJD on the other hand is transmissible to humans through exposure to the
BSE prions, commonly known as “mad cow disease” (Hornlimann, Riesner, and Kretzschmar,
196).
Creutzfeldt-Jakob Disease: Incubation period
The incubation period could only be recorded for forms of CJD that are acquired. In the
case of iCJD when it is caused by direct intracerebral contact of infectious material, for example,
during neurosurgery, the incubation period is 1.5-1.6 years (Hornlimann, Riesner, and
Kretzschmar, 196). When infected during a dura mater transplant the incubation period is 9 years
(Hornlimann, Riesner, and Kretzschmar, 196). When a patient acquired the disease through
hormone injections the incubation period is a whopping 12-13 years (Hornlimann, Riesner, and
Kretzschmar, 196).
Creutzfeldt-Jakob Disease: Symptoms
General symptoms of “classical” CJD include rapidly progressive dementia and
myoclonus which is abrupt spasm of a muscle or group of muscles (Hornlimann, Riesner, and
Kretzschmar, 197). Patients experience pyramidal or extrapyramidal symptoms such as
spasticity, hyperreflexia which is an abnormal overreaction of the nervous system to a
stimulation (Capellone and Zieve, Autonomic Hyperreflexia). They also experience symptoms
such as ataxia (loss of coordination) or visual symptoms such as akinetic mutism which is
apparent alertness and normal eye movements but no other voluntary motion (Hornlimann,
Riesner, and Kretzschmar, 197). Risk factors for sCJD and iCJD includes specific genetic factors
that increase the susceptibility (Hornlimann, Riesner, and Kretzschmar, 199). Genetic history
causes fCJD while iCJD is caused by contaminated equipment. Risk factors for vCJD includes
cows infected with BSE (Hornlimann, Riesner, and Kretzschmar, 199).
Prions are responsible for all these degenerative diseases. Kuru is especially distinctive
for its symptom of horrible laughter. GSS and fCJD could both be genetically passed down
through relatives. There are so many forms of CJD including acquired CJD and iCJD caused by
pseudo doctors. Although the prion protein could cause all of these diseases and cause their
patients to undergo terrible symptoms, it is very rare to get these diseases. Diseases caused by
prions are not easily transmissible from person to person so they are unlikely to cause a
worldwide epidemic. Just try not to eat infected brains, stay away from pseudos, and hope it’s
not in your genes.
Bibliography
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Hornlimann, Beat, Detlev Riesner, and Hans Kretzschmar, eds. Prions in Humans and
Animals. Berlin: Walter De Gruyter, 2007. Print.
Morrison, Douglas R. O., ed. Prions and Brain Diseases in Animals and Humans. New
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