What Is Huntington's Disease? What Causes Huntington's Disease?

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Main Category: Huntingtons Disease
Also Included In: Neurology / Neuroscience;  Caregivers / Homecare;  Palliative Care / Hospice Care
Article Date: 02 Aug 2009 - 0:00 PDT

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Huntington's disease is an incurable, hereditary brain disorder. It is a devastating brain disorder for which there is no currently 'effective' treatment. Nerve cells become damaged, causing various parts of the brain to deteriorate. The disease affects movement, behavior and cognition - the affected individuals' abilities to walk, think, reason and talk are gradually eroded to such a point that they eventually become entirely reliant on other people for their care. Huntington's disease has a major emotional, mental, social and economic impact on the lives of patients, as well as their families.

It used to be called Huntington's Chorea, because the involuntary movements made by patients with the disease can appear to be like jerky dancing - "chorea" comes from the Greek word choreia meaning "dancing". The English word "choreography" also comes from the Greek word choreia.

Huntington's disease (HD) affects both men and women equally and more commonly appears during middle-age. According to the Department of Health, UK, there are about 6,000 people in the UK with the disease. The Huntington's Society of America says 1 in every 10,000 Americans has the disease - 30,000 people. It is estimated that at least 150,000 other Americans have a 50% risk of developing HD, while thousands of their relatives carry a degree of risk too.

Prevalence of the disease varies according to ethnic ancestry - people with Asian or African inheritance have a 1 in 1,000,000 risk of becoming affected, while the risk for Caucasian people is 70 to 100 times higher.

The J. David Gladstone Institutes, Taube Philanthropies and the Koret Foundation initiated a groundbreaking research program aimed at preventing, treating, or curing Huntington's disease by the year 2020.

What are the signs symptoms of Huntington's disease?

Sings and symptoms can appear at any age, but most commonly do so between the ages of 35 and 55 years. They will progressively worsen for ten to twenty years until the patient ultimately dies.

A sign is what the doctor can detect, such as involuntary movements, or a rash. A symptom is what the patient tells the doctor, such as dizziness, or insomnia.

How sings and symptoms evolve and which ones appear first may vary from person to person. Some may develop depression before suffering problems with motor skills.

Initial symptoms may initially be either ignored or attributed to something else for some time by most patients and their family and friends. This is more likely if people are not aware that Huntington's disease exists in their family. Symptoms may initially include mood swings and peculiar behavior.

Subtle signs can help doctors predict that a person will develop Huntington's disease in the next few years, scientists at the University of Iowa revealed.

It is not uncommon for some people to deny they have the condition and take a long time to come to terms with the diagnosis.

Possible early signs and symptoms

Below is a list of early signs and symptoms which may be relevant in some cases. It is important to remember these may vary depending on the individual:

• Slight uncontrollable movements
• Clumsiness
• Stumbling
• Some slight signs of lack of emotion
• Lack of focus, slight concentration problems
• Lapses in short-term memory
• Depression
• Mood changes - this may include antisocial behavior and aggression

Distressing for those who don't know - if family and friends don't know what is going on the impact on relationships and family life can be demoralizing, distressing and sometimes shocking. Unexpected temper outbursts directed at a partner from somebody who has hitherto been regarded as warm, caring and loving is frightening and confusing.

Friends and family may get the impression that an individual with HD is lazy - but it is not the case. HD typically affects a person's personality in such a way that they come over as unmotivated, unfocussed, lethargic, and lacking in initiative.

Unnecessarily worrying for those who do know - those who do know they are at risk may become concerned when they wonder whether an HD sign has emerged. Examples may include dropping something, suddenly becoming angry, forgetting somebody's name, or stumbling. These 'signs' are things all of us do from time to time.

In both cases, whether you are aware of the risk, or have no idea what is happening, talking to your GP (general practitioner, primary care physician) is advisable. The GP may refer the patient to a neurologist.

As Huntington's disease progresses

As the disease progresses problems will become more severe. These will include:

Physical changes not including uncontrollable movements


• Difficulty in speech - individuals with Huntington's have problems putting thoughts into words and slur their speech


• Weight loss - often a cause of complications because the patient becomes weaker. Although most people with HD generally have good appetites, the muscles in the mouth and the diaphragm may not work properly, making the whole experience of eating seem cumbersome, frustrating and messy.


• Feeding problems - as coordination gets worse the person with HD may spill and drop food.


• Swallowing difficulties get gradually worse - chocking on food and drink. Choking tends to occur more when the liquid is thin, like water. During the later stages choking becomes a major concern.

Uncontrollable movements


• Uncontrollable movements of the face.


• Jerking of parts of the face and the head.


• Flicking or fidgety movements of the arms, legs and body.


• Lurching and stumbling - caused when movements move from one area of the body to another.


• As HD progresses the uncontrollable movements occur more often and with usually with more intensity.


• Eventually the movements may become slower as the muscles become more rigid.

Emotional changes - sometimes changes may alternate sporadically


• Aggression.
• Anger.
• Antisocial behavior.
• Apathy.
• Depression.
• Excitement.
• Frustration.
• Lack of emotion becomes more apparent.
• Moodiness.
• Stubbornness.

Cognitive changes


• Loss of initiative.
• Loss of organizational skills.
• Disorientation.
• Problems focusing.
• Problems focusing on more than one thing at a time.

Some patients and carers comment that the psychological changes are more of a problem than the physical ones. Although some psychological changes are caused by the disease, frustration at not being able to do things which used to be easy can become depressing.

In the later stages the person will require total round-the-clock nursing care. The patient will not be able to walk or talk, although he/she will usually understand most of what is being said and will be aware of friends and family members.

In the majority of cases people die from a complication of Huntington's disease, such as pneumonia, choking, or another infection, rather than Huntington's itself.

Weight loss can bring with it worsening symptoms, as well as weakening the patient's immune system, which makes him/her more vulnerable to infections and other complications. Throughout all the stages of Huntington's disease it is important to adjust the patient's diet to ensure adequate food intake.

Genetic testing

As Huntington's disease is inherited dominantly, a child of a parent who has/had the disease has a 50% chance of inheriting the defective gene. Often the disease affects several generations. Genetic testing for HD became possible in 1993 when the first non-sex-linked dominant disease gene was found.

If you have a family history of Huntington's you can discuss with your doctor about genetic testing - it will determine whether or not you carry the defective gene. Some people find the uncertainty of not knowing stressful and unpleasant. On the other hand, finding out they have the gene and will develop Huntington's is distressing too. If you are not sure what to you, you should consider talking to a genetic counselor who will help you think the whole thing through.

In the UK fewer than 1 in 5 people at risk of having the faulty gene choose to undergo genetic testing. A study published in the British Medical Journal reported that individuals with a family history of genetic disease are frequently discriminated by their relatives, friends and also by insurance companies.

What causes Huntington's diseases?

Genes and chromosomes

Genes are made up of DNA. They are packaged into strands we call chromosomes. Genes are the instructions for making any living thing: humans, bacteria, plants, animals, etc. Humans have 23 pairs of chromosomes - 46 in all.

The faulty gene that causes Huntington's disease is found on chromosome number 4. A normal copy of the gene produces huntingtin, a protein. The faulty gene is larger than it should be and produces a larger form of huntingtin.

Some of our brain cells are sensitive to the larger form of huntingtin - it undermines their function and eventually destroys them. Scientists are not sure exactly how this happens. Johns Hopkins brain scientists have figured out why a faulty protein accumulates in cells everywhere in the bodies of people with Huntington's disease, but only kills cells in the part of the brain that controls movement, causing negligible damage to tissues elsewhere. The answer lies in one tiny protein called "Rhes" that's found only in the part of the brain that controls movement.

A person with the Huntington's gene has one good copy of the gene and one faulty copy of the gene. His/her child will inherit either the good copy or the faulty one. The child who inherits the good copy will not develop Huntington's disease, while the child who inherits the faulty copy will. The child has a 50% chance of inheriting the faulty gene. If the child inherits the faulty gene, each of his/her children will have a 50% chance of inheriting the faulty gene.

Doctors and scientists refer to the disease as an autosomal dominant disorder - only one copy of the faulty gene, inherited from either the mother or the father, is necessary to produce the disease.

A child who does not inherit the faulty gene will not develop HD and cannot pass it on to his/her children. A child who inherits the faulty gene will develop HD if he/she reaches the age when symptoms are due to emerge.

3% of people with Huntington's disease apparently have no family history of it. Some of them were adopted and never knew whether their parents had it. Others may have had a parent with the faulty gene who died from something else before reaching the age when symptoms would have emerged. In some cases there may be a new error in the gene - a mutation (it has to start somewhere).

British scientists found high levels of an inflammation-causing protein called IL-6 in the blood of affected individuals more than a decade before they were expected to develop the nervous system symptoms of the Huntington's disease. It has always been presumed that brain deposits of the mutant protein that causes the disease, called huntingtin, lured an overactive immune response. But since the immune cells that make IL-6 also make huntingtin, it's possible that mutant huntingtin might wrongly set these cells on attack mode throughout the body. Early intervention strategies to suppress the production of IL-6 might thus stave off brain destruction.

How is Huntington's disease diagnosed?

German scientists discovered that profound changes (comparable to those seen in late-stage HD) actually occur well before any disease symptoms show up, and most of the changes are confined to a specific stage during disease progression.

The doctor will examine the patient; ask about family history, personal medical history, and recent emotional and intellectual changes. The doctor may also recommend a psychiatric evaluation.

Sometimes doctors order imaging tests to identify any changes in the patient's brain structure, as well as to rule out other disorders. This may include either a CT (computer tomography) scan or an MRI (magnetic resonance imaging) scan.

• Genetic Testing to confirm diagnosis
  
  If it is known that there is a family history of Huntington's disease to doctor will recommend genetic testing to confirm the diagnosis. If there is no family history the doctor may recommend genetic testing if other possible diseases or conditions have been ruled out. Many countries have a minimum age for genetic testing for HD - in the USA and the UK it is 18 years (unless there is a medically compelling reason to test a minor). If someone is found to have the faulty gene but does not yet have symptoms, it is impossible to predict when they will appear.
  
  In the UK a GP (general practitioner) will arrange for an appointment at a regional genetic clinic. Genetic counseling will be offered free of charge (UK) and two blood samples will be taken. DNA in the blood sample is extracted and analyzed.


• Genetic tests in pregnancy
  
  A genetic test can be done on the 11th week of pregnancy. The test will determine whether the embryo has the faulty gene. Genetic counseling is an integral part of the process. Most countries' guidelines say that the pregnant woman should be accompanied to all testing sessions by a companion (not a sibling).


• Preimplantation genetic diagnosis
  
  If a partner has the faulty gene, it is possible to have in-vitro fertilization (IVF) treatment. The embryo is then genetically tested in a laboratory and is only implanted into the woman if it does not have the faulty gene.

What is the treatment for Huntington's disease?

Huntington's disease is incurable. There is no current treatment that can reverse its progression or slow it down.

Scientists at UT Southwestern Medical Center found that man-made molecules that selectively interfere with protein production can stop human cells from making the abnormal molecules that cause Huntington's disease. They added that "The work has been done only in cultured cells, and it will take years before the effectiveness of this process can be tested in patients."

Some symptoms can be managed with medication and therapies.

Medications

• Tetrabenazine (Xenazine) - in August 2006 the FDA (Food and Drug Administration), USA approved tetrabenazine for the treatment of jerky, involuntary movements (chorea) associated with Huntington's disease - the first to be specifically approved for this in the country. The compound has been known since the 1950s. It promotes the early metabolic degradation of the neurotransmitter dopamine.
  
  Side effects include:
  
  
  • Drowsiness.
  • Nausea.
  • Restlessness.
  • Dizziness.
  • Depression - reported in roughly 15% of those who take the medication.

Tetrabenazine should not be taken by patients diagnosed with depression, especially people with suicidal thoughts.


• Sometimes clonazepan (Klonopin) and haloperidol and clozapine (Clorazil) are prescribed to control movements, violent outbursts and hallucinations. These drugs may cause sedation, as well as stiffness and rigidity.


• Fluoxetine (Prozac, Sarafem), sertraline (Zoloft) and nortriptyline (Pamelor), may be prescribed for depression and some of the obsessive-compulsive disorders that are associated with HD.


• For extreme emotions and mood swings lithium (Eskalith, Lithobid) may be prescribed.

Speech therapy

Speech therapy can help patients who find strategies to utter words and phrases and communicate in a more effective way.

Physical and occupational therapy

Better muscle strength and flexibility can be achieved with a good physical therapist. Strength and flexibility will help the patient's balance and reduce the risk of falling. An occupational therapist can help the patient devise strategies for coping with concentration and memory problems, as well as making the home safer.

Gene Therapy

This is still in its infancy but some promising research is going on in many parts of the world.

• Researchers from the University of Southern California have taken an important first step toward protecting against Huntington disease using gene therapy. Kelvin J. A. Davies, professor of gerontology in the USC Davis School of Gerontology, said "Our findings allow for the possibility that controlled over-expression of RCAN1-1L might in the future be a viable avenue for therapeutic intervention in Huntington disease patients."


• Howard Hughes Medical Institute researchers designed tiny RNA molecules that shut off the gene that causes Huntington's disease without damaging that gene's healthy counterpart, which maintains the health and vitality of neurons.

Strengthening antioxidant defenses (potential therapy?)

Therapeutic strategies to strengthen antioxidant defenses could help to prevent the progression of Huntington's disease, scientists in Spain revealed. Their research was carried out using human brain samples obtained post mortem from people affected by HD, which were compared with samples from control patients who had died from unrelated illnesses or other causes.

The caregiver (UK/Ireland/Australia: carer)

Caregiving can become time-consuming and mentally and physically exhausting. Caring for somebody with HD, especially if you are a lone caregiver, will become increasingly so. If you can afford it, get somebody in to help out with either the household chores or the physical care of the person with HD. Inquire with local health agencies, your doctor, about support groups, assistance programs, nursing assistance, and other services.

Caregivers have a higher risk of becoming ill themselves, partly because of the stress involved in caregiving, and also because most caregivers are elderly themselves. If you are a caregiver it is important you see your doctor whenever you don't feel physically or mentally well. Joining a support group may give you the opportunity to "share the burden" which often helps.

During the final stages of Huntington's disease the caregiver may not be able to provide all the care the HD person needs. There are long-term facilities that can do this.

Written by Christian Nordqvist


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