what is huntington's chorea?

Question

What is huntington's chorea? can someone give me a brief description and point me to a good site which covers it in detail. please don't just say wikipedia because i know it. i'm only 13 so please not tooo confusing. its for a presentation that must last for 3-5 minutes. Thx

Answer 1

Ok, well the last response was probably way too much for you to handle, so I'll try and simplify this complex disorder.

Huntington's chorea is a manifestation of Huntington disease, which is itself caused by atrophy of 2 structures in the brain, called the caudate and putamen. Now, these structures are responsible for motor inhibition, which basically suppresses unwanted movement that would occur with all of us if we did not have a caudate and putamen.

The chorea is observed as involuntary and ballistic movements that is without any clear purpose. "Chorea" means "dance", and is called such because I guess someone thought that the Huntington-patient's gait somewhat resembled a dance -- I've seen it, and it's kind of like if all your movements were exaggerated and you weren't able to stop your limbs from overshooting where they were going. These involuntary movements are often incorporated into the patient's normal movements in an attempt to obscure the disease.

Other symptoms (besides chorea) include changes in personality, which may include irritability, suspiciousness, and impulsive or eccentric behavior.

Huntington disease is caused by an autosomal-dominant triplet-repeat on chromosome 4, and is not manifest until about 30-40 years of age. There is currently no cure, though medications can help manage the symptoms.

Answer 2

costly Esme, it seems such as you have been performing some self diagnosing on the information superhighway. provide up doing it, it relatively is a waste of time. bypass see a doctor and get a robust examine-up with blood artwork, and tell him all your warning signs. There may be an straight forward explanation as to why you're shaking and you have become your self all labored up and under pressure approximately Huntington's! On Monday, make an appointment.

Answer 3

Chorea- flicking movements.3 biochemically distinct pathway operate in a balanced manner in the basal ganglia- of our brain. 1. Nigro striatal dopaminergic, 2. intrastriatal cholinergic & 3. intrastriatal GABAergic system. In this disease, there is loss of 2 & 3. This leads to loss of inhibition so hypokinetic features set in. It is an autosomal dominant disorder, onset- bet 30 & 50 age grp. Abnormal gene located in chromosome 4 normally contains 11 to34 CAG repeats but in this condition, increased to 42 to 86 or more copies. Hope this helps u Mbolt! 4 further reference look up to ally ally1!

Answer 4

Try http://www.webmd.com/. Good luck: Blueladybug

Answer 5

Huntington's disease (HD), also known as Huntington disease and previously as Huntington's chorea and chorea maior, is a rare inherited neurological disorder affecting up to 8 people per 100,000. It takes its name from the Ohio physician George Huntington who described it precisely in 1872 in his first medical paper. HD has been heavily researched in the last few decades and it is one of the first inherited genetic disorders for which an accurate test can be performed.

HD is caused by a trinucleotide repeat expansion in the Huntingtin (Htt) gene; and is one of several polyglutamine (or PolyQ) diseases. This expansion produces an altered form of the Htt protein, mutant Huntingtin (mHtt), which results in neuronal cell death in select areas of the brain.

HD's most obvious symptoms are abnormal body movements called chorea and a lack of coordination, but it also affects a number of mental abilities and some aspects of personality. These physical symptoms commonly become noticeable in a person's forties, but can occur at any age. If the age of onset is below 20 years then it is known as Juvenile HD. Being a genetic disorder, there is currently no cure, but the symptoms are managed with medication and appropriate care.

Signs and symptoms

There is no sudden loss of abilities or exhibition of symptoms, but there is a progressive decline. Physical signs are usually the first noticed, but it is unknown how long before this that cognition and psychiatric condition are affected. Physical symptoms are almost always shown, cognitive symptoms are exhibited differently from person to person, and psychiatric problems may not be evident at all.

Physical

Most people with HD eventually exhibit chorea, which is jerky, random, uncontrollable, rapid movements, although some exhibit very slow movement and stiffness (bradykinesia, dystonia). These abnormal movements gradually increase as the disease progresses, initially exhibited as general lack of coordination and an unsteady gait. This causes problems with loss of facial expression (called "masks in movement") or exaggerated facial gestures, ability to sit or stand stably, speech, chewing and swallowing (which can lead to weight loss if diet or eating methods are not adjusted accordingly[citation needed]), and loss of determination. In the later stages of the disease, speaking, eating and mobility are extremely difficult, if not impossible, and full-time care is required.

Cognitive

Selective cognitive abilities are progressively impaired, whereas others remain intact. Abilities affected are executive function (planning; cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions, and inhibiting inappropriate actions), psychomotor function (slowing of thought processes to control muscles), speech (but not actual language skills), perceptual and spatial skills of self and surrounding environment, selection of correct methods of remembering information (but not actual memory itself), and ability to learn new skills, depending on the affected parts of the brain

Psychopathological

Psychopathological symptoms vary more than cognitive and physical symptoms, and may include anxiety, depression, a reduced display of emotions called blunting, egocentrism, aggressive behaviour, compulsivity which can cause addictions such as alcoholism and gambling, or hypersexuality.

Many patients are unable to recognize expressions of disgust in others and also don't show reactions of disgust to foul odors or tastes.[1] The inability to recognize disgust in others appears in carriers of the Huntington gene already before the disease has broken out.[2] A number of related studies have been published.[3]

Causes

HD is inherited in an autosomal dominant fashion.The gene involved in HD, called the HD gene, is located on the short arm of chromosome 4 (4p16.3). The end of the HD gene has a sequence of three DNA bases, cytosine-adenine-guanine (CAG), that is repeated multiple times (i.e. ...CAGCAGCAG...), this is called a trinucleotide repeat. CAG is the codon for the amino acid glutamine. A sequence of fewer than 40 glutamine amino acid residues is the normal form, producing a 348 kDa cytoplasmic protein called huntingtin (Htt). If there are more repeats of CAG than this, a mutated form of Htt that causes the disease, mHtt, is produced. The continuous build up of the mHtt molecules in neuronal cells causes them to die off in selected regions of the brain. The speed of cell degeneration is generally proportional to the number of extra CAG repeats, also causing earlier onset of symptoms.

HD is autosomal dominant, needing only one affected allele from either parent to inherit the disease. Although this generally means there is a one in two chance of inheriting the disorder from an affected parent, the inheritance of HD and other trinucleotide repeat disorders is more complex.

When the gene has more than 35 copies of the repeated trinucleotide sequence, the DNA replication process becomes unstable and the number of repeats can change in successive generations. If the gene is inherited from the mother, the count is usually similar, but tends to increase if inherited from the father.[4] Because of the progressive increase in length of the repeats, the disease tends to increase in severity and have an earlier onset in successive generations. This is known as anticipation.

Mechanism

The continuous build up of mHtt molecules in neuronal cells causes cell death, especially in the frontal lobes and the basal ganglia (mainly in the caudate nucleus). Degeneration of the striatum (a part of the brain consisting of the caudate nucleus and the putamen) can be found. There is also neuronal loss and astrogliosis, as well as loss of medium spiny neurons, a GABAergic (the chief inhibitory neurotransmitter in the vertebrate central nervous system) result. This results in the selective degeneration of the indirect (inhibitory) pathway of the basal ganglia, via the lateral pallidum and the subthalamic nucleus coupled pacemaker system. Intranuclear inclusions that stain for ubiquitin and Htt can be seen, as well as Htt in cortical neurites.

It is suspected that the cross-linking of Htt results in aggregates which are toxic, causing a mitochondrial dysfunction in the proteasome system, leading to neurons being damaged by excitotoxicity and oxidative stress.

The exact link between CAG repeats that produce mHtt and mitochondrial failure is unknown. There is evidence that aggregates may trap critical enzymes that are involved in energy metabolism.[citation needed] Some think that the cause of cell death is the splitting of the lysosome so that the hydrolytic enzymes within it are released. [citation needed]This will cause the cell membrane to split and the cell to die.

While theories as to how the mutation brings about disease remain diverse and speculative, researchers have identified many specific subcellular abnormalities associated with mHtt, as well as unusual properties of the protein in vitro. Just as one example, in 2002, Max Perutz, et al discovered that the glutamine residues form a nanotube in vitro, and the mutated forms are long enough in principle to pierce cell membranes.[5]

In the June 16, 2006 issue of Cell, scientists at the University of British Columbia (UBC) and Merck Labs presented findings that the neurodegeneration caused by mHtt is related to the caspase-6 enzyme cleaving the Htt protein. Transgenic mice that have caspase-6 resistant Htt did not show effects of HD.[6] The researchers found "substantial support for the hypothesis that cleavage at the caspase-6 site in mHtt represents a crucial rate-limiting event in the pathogenesis of HD.... Our study highlights the importance of preventing cleavage of htt at this site and also reinforces the importance of modulating excitotoxicity as a potential therapeutic approach for HD." In essence, scientists have managed to prevent the appearance of HD in genetically modified mice. Dr. Marian DiFiglia, a world-renowned HD researcher and neurobiologist at Harvard University, called this find "very important" and "extremely intriguing".[7]

Diagnosis

To determine if initial symptoms are evident, a physical and/or psychological examination is required. The uncontrollable movements are often the symptoms which cause initial alarm and lead to diagnosis; however, the disease may begin with cognitive or emotional symptoms, which are not always recognized. Every child of a person with HD has a fifty percent chance of inheriting the gene and the disease. Pre-symptomatic testing is possible by means of a blood test which counts the number of repetitions in the gene. A negative blood test means that the individual does not carry the gene, will never develop symptoms, and cannot pass it on to children. A positive blood test means that the individual does carry the gene, will develop the disease, and has a 50% chance of passing it on to children. A pre-symptomatic positive blood test is not considered a diagnosis, because it may be decades before onset. Because of the ramifications on the life of an at-risk individual, with no cure for the disease and no proven way of slowing it, several counseling sessions are usually required before the blood test. Unless a child shows significant symptoms of the juvenile form, children under eighteen cannot be tested. The members of the Huntington's Disease Society of America strongly encourage these restrictions in their testing protocol. A pre-symptomatic test is a life-changing event and a very personal decision. For those living in America, there is a list of testing centers available on the HDSA homepage [8] and embryonic genetic screenings are also possible, giving gene-positive or at-risk individuals the option of making sure their children will be clear of the disease. Expense and the ethical considerations of abortion are potential drawbacks to these procedures. The full pathological diagnosis is established by a neurological examination's findings and/or demonstration of cell loss, especially in the caudate nucleus, supported by a cranial CT or MRI scan findings.

Management

There is no treatment to fully stop the progression of the disease, but symptoms can be reduced or alleviated through the use of correct medication and care methods.

Medication

There are treatments available to help control the chorea, although these may have the side effect of aggravating bradykinesia or dystonia.

Other standard treatments to alleviate emotional symptoms include the use of antidepressants and sedatives, with antipsychotics (in low doses) for psychotic symptoms. Care needs to be taken with antipsychotic usage as people suffering psychotic symptoms of organic origin are often more sensitive to the side effects of these drugs.

Nutrition

Nutrition is an important part of treatment; most HD sufferers need two to three times the calories than the average person to maintain body weight, so a nutritionist's advice is needed (the normal population's average daily intake is approximately 2000 calories for women and 2500 for children and men).

Speech therapy can help by improving speech and swallowing methods. This advice should be sought early on, as the ability to learn is reduced as the disease progresses.

To aid swallowing, thickener can be added to drinks. The option of using a stomach PEG is available when eating becomes too hazardous or uncomfortable, this will reduce the chances of pnuemonia due to aspiration of food and increase the amount of nutrients and calories that can be ingested.

EPA, an Omega-III fatty acid, slows and possibly reverses the progression of the disease. It is currently in FDA clinical trial, as Miraxion© (LAX-101), for prescription use. Clinical trials utilize 2 grams per day of EPA. In the United States, it is available over the counter in lower concentrations in Omega-III and fish oil supplements.

A calorie restrictive diet delays the onset of symptoms in HD mice.[9]

Potential Treatments

Trials and research are conducted on Drosophila fruit flies and mice that have been genetically modified to exhibit HD, before moving on to human trials.

Research is reviewed on various websites for HD sufferers and their families, including the Huntington's Disease Lighthouse, Hereditary Disease Foundation, and Stanford HOPES websites. Primary research can be found by searching the National Library of Medicine's PubMed. Clinical trials of various treatments are ongoing, or yet to be initiated. For example, the US registrar of trials has nine that are currently recruiting volunteers.[10]

Gene silencing

The most hopeful prospective treatment currently studied is based on gene silencing. Since HD is caused by expression of a single gene, silencing of the gene could theoretically halt the progression of the disease. One study with a mouse model of HD treated with siRNA therapy achieved 60% knockdown in expression of the defective gene. Progression of the disease halted.[11] Full recovery of motor function is observed in late stage Tet/HD94 mice after addition of doxycycline.[12]

Others

Folding@Home running on a PS3Other agents and measures that have shown promise in initial experiments include dopamine receptor blockers, creatine, CoQ10, the antibiotic Minocycline, exercise, antioxidant-containing foods and nutrients, antidepressants (notably, but not exclusively, selective serotonin reuptake inhibitors SSRIs, such as sertraline, fluoxetine, and paroxetine) and select Dopamine antagonists, such as Tetrabenazine.

Pig cell implants in HD trial: Living Cell Technologies in New Zealand has attempted trials with positive results in primates, but is yet to conduct a human trial.[13]

The Folding@home project is the second largest distributed processing project on the internet. It models protein folding and HD is listed amongst the potential benefactors of its results.

Prognosis

Onset of HD seems to be correlated to the number of CAG repeats a person has in their HD gene. Generally, the higher the number of repeats the sooner is the onset.[14] The number of repeats may change slightly with each successive generation, so that the age of onset may vary as well. Symptoms of Huntington’s disease usually become noticeable in the mid 30s to mid 40s.

Juvenile HD has an age of onset anywhere between infancy and 20 years of age. The symptoms of juvenile HD are different from those of adult-onset HD in that they generally progress faster and are more likely to exhibit rigidity and bradykinesia (very slow movement) instead of chorea.

Mortality is due to infection (mostly pneumonia), fall-related injuries, other complications resulting from HD, or suicide (The suicide rate for HD sufferers is much greater than the national average.[15]), rather than the disease itself. Life expectancy is generally between 10 and 25 years after the onset of obvious symptoms.

Other Websites:

http://www.huntington-assoc.com/
http://www.hdlighthouse.org/
http://www.huntingtonproject.org/
http://www.stanford.edu/group/hopes/