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.
