Etiology
HD is a fatal disease caused by a genetic fault on chromosome 4 one of the 22 non-sex-linked (autosomal) pairs of chromosomes, placing men and women at equal risk of acquiring the disease, and it is the gene that is responsible for the production of Huntingtin protein as discovered in 1993 (Huntington’s disease Association 2009). For this disease to develop, instead of the Huntingtin gene (HTT) normally coding for the in sequence production of Huntingtin protein, it codes for a mutant Huntingtin protein (mHTT) thus causing the disease. HD is inherited as an autosomal dominant disease, with one dominant gene inheritance from any of the parents there is an automatic clinical syndrome on the offspring, but recessive genes must be acquired from both parents (Amanda & Greenberg, 2008).
Background information and inheritance of Huntington’s disease
Huntington’s disease (HD) is a clinical illness that has been associated with a couple of hereditary disorders of the Central Nervous System (CNS), and the disease condition usually develops in the late stage of human development with various clinical symptoms intensified in neurological and psychiatric effects. The syndrome does not have any sex preferences factors and thus it equally affects men and women and it has been originally referred to as Huntington’s chorea (HC). This, therefore, shows that Huntington’s disease is highly spread through the inheritance of genes from a parent to offspring with a probability of 0.5 of faulty gene inheritance and the genetic mutation can be passed down through generations. Degenerative impact on the neurons in the basal ganglia, cerebral cortex, and other areas of the brain, causes steady bodily, emotional, and mental changes on the affected people and thus exhibiting the clinical syndrome HD, which is classically characterized by uncontrolled involuntary movements (chorea), loss of intellectual abilities and declined cognitive activities of the body (dementia). This is because the affected centers in the brain are responsible for vital functions, such as locomotion, perception, reminiscence, and coordination. HD is an example of many syndromes that demonstrates several trinucleotide repeat disorders caused by the length of a repeated section of a gene exceeding the normal range (Office of Communications and Public Liaison Jan 05, 2009).
Demographics
The HD syndrome has spread globally and on researches being done currently HD, infection has shown a great increment in the previous few decades. Worldwide the late development has averagely indicated that up to 7 people in 100,000 adults manifest the clinical condition, despite some segregated areas having higher indices of preference. HD has shown a very gradual development of clinical syndrome with response to aging, and average it starts at the age of 35-44 years though juvenile Huntington Disease can be seen at the age of fewer than 20 years (free Encyclopedia on Huntington Disease, 2009). Currently, an estimated population of more than 15,000 Americans is exhibiting the clinical disease HD (Office of Communications and Public Liaison Jan 05, 2009). Whites have shown to have high preference rates for acquiring the hereditary disorder as compared to their black counterparts, for instance in South Africa so far it has been confirmed that over 200 white and colored family cases while only 50 black cases have been reported by South African’s molecular genetics diagnostic laboratories at Wits National Health Laboratory Service (NHLS) and UCT NHLS (Amanda & Greenberg, 2008).
HD, for example, has occupied many white people populations and in Europe, it’s approximated that about 4-8/100 000 individuals are affected, a high frequency in these white due to founder effect. The black South Africans show a disease preference of fewer than 0.1 persons per million people, a level which is slightly above the Juvenile occurrence. For instance, in the United States, the overall prevalence of HD is about 1 in every 10,000-20,000 persons. The disease begins often in mid-adulthood, although the age of onset varies greatly, usually disease onset is at 30-55 years of age despite Juvenile cases appearing in around 0.1 of all cases reported (California aging and Memory Center 2009).
First recorded diagnose or discovery
This nervous disorder derived its name from the founder of the disease who was known by the name George Huntington, an American physician who published an outstandingly accurate portrayal in 1872. Initially in 1860, HD was described as a unique illness (believed to be a form of witchcraft) by a Norwegian district medical doctor, Johan Christian Lund, in a remote and rather secluded area of Setesdalen, where there was a high occurrence of dementia linked with a pattern of jerking locomotion disorders that tended to scamper in families (here the disease is commonly referred to as Setesdalsrykkja – Norway). Later on a marker for the altered DNA strand causing the HD was established in 1983, followed by a discovery of an individual causal agent, the mutant Huntingtin protein-codin gene (mHTT), leading to the development of an accurate test for the disease (Office of Communications and Public Liaison Jan 05 2009). Due to this availability Huntington genetic disease test and the show of analogous symptoms like other neurological disorders, there has been a great advancement in the research of the disease in the recent past.
Symptoms
Initially, the first symptoms consist of varied changes in personality, such as temper swings, petulance, signs of apathy, sadness, irritation among others may show different forms of hostility. Other patients develop slight disorderly muscular movements, awkwardness and inelegance, diminished concentration, temporal memory lapses, despair, and changes of mood, sometimes including aggressive or antisocial behaviors since the disease demolishes most of the cognitive responses (Huntington’s disease Association 2009). In progress of this disease, the patient experiences ever more difficulty in concentration on intellectual tasks. Manifestations of Chorea (characterized as jerky, random and uncontrollable movements) are shown at different points of the ailment, as it begins as hysterical movements of the extremities, head, or trunk that is dependent on the patient and may become gradually worse (California aging and Memory Center 2009). These signs may be followed by other nervous signs which include twitchy movements, restlessness, ineptness, or loss of body balance and the affected person may show in coordination and even fall down.
Further progress of the HD can go as far as where the patient’s speech is garbled and abolishment of vital functions, such as swallowing leading to the development of dysphagia, patients develop a poor appetite, speaking also becomes difficult including changes of gait and difficulty in walking, signs which worsen with the development of the disease. There is poor recognition but some of them manifest awareness to the immediate environment and possess good expressions of emotions. The disease spread in a period of about 10 to 30 years after the onset of the clinical disease up to death, but the causes of death are infections, falling injuries, and additional disease complications (Office of Communications and Public Liaison Jan 05, 2009). Dysphagia and difficulty in eating usually tend to cause emaciation and dejection of the patients and this, later on, may lead to undernourishment and starvation, this enhances malnutrition leading to sleep cycle disturbances, including sleeplessness and fast eye movement nap alterations usually follow. Meanwhile Juvenile HD in general progresses more rapidly than the actual illness in adults and is more probable to show signs of stiffness and bradykinesia instead of chorea as seen in the adult patients and frequently includes convulsions. This model of deficits is a subcortical dementia syndrome different from typical cognitive affectation of cortical dementias as shown by Alzheimer’s disease. Psychiatric symptoms vary to a great extent; likely neuropsychiatric manifestations are nervousness, dejection, a condensed display of emotions, egocentrism, belligerence, and irrational behavior, which causes or worsens addictions such as alcoholism and making of bets or hypersexuality (Oliver, 2008).
Diagnosis
Medical officers usually neurologist uses the pedigree/genealogy to rule out all other differentials and honest information on the medical history of the family should be required from the patient. Also, some functional tests should be performed such as intellectual or emotional problems associated with HD and will test the person’s audibility and balance, eye movements, strength and coordination, involuntary movements, sensory responses, reflex actions, locomotion, and mental status before taking samples for several laboratory tests. These includes Computer Tomography (CT), Magnetic Resonance Imaging (MRI) and the recently developed Positron Emission Tomography (PET) techniques providing good images of brain’s shrinkage of affected parts of the brain that is caudate nuclei and putamen plus swelling of fluid-filled cavities within the brain ventricles thus giving the definitive diagnosis of the syndrome.
Treatments
There is no conventional treatment or cure for the Huntington’s disease, but many ways have been used to manage HD symptoms. This is to abolish the clinical symptoms and signs what is referred to as symptomatic therapy and supportive care. For the supportive care, people with this disease should visit Psychiatrists for genetic counseling once positive diagnosis is achieved and also to offer speech therapy thus enhancing good communication. It’s necessary again for these people to be fit and engaging in exercises, but in a safe environment free of sharp objects, good nutrition including especially vitamins and other nutritional supplements in their diet, accessible to plenty of clean drinking water to avoid chances of dehydration and their food should be thinned owing to disphagia and gastrointestinal problems which may cause incontinence, choking or constipation. Some drugs such as tetrabenazine have been used in the treatment of Huntington’s chorea, and this is due to its antagonistic effects on uncontrolled involuntary movements.
In symptomatic therapy of HD, clinicians use drugs such as antipsychotic drugs (e.g. haloperidol and clonazepam) which help the patient in alleviating choreic movements exhibited by HD patients and similarly control delusions, hallucinations, and vicious outbursts. However these antipsychotic drugs are contra indicated for dystonia (muscle contraction associated with HD) since the drugs may worsen the situation through severe stiffness and rigidity. Other than these effects, under medication the patient can develop severe side effects, including sedation therefore encouraging use of possible lowest doses. For depression, the patient’s indication should comprise fluoxetine, sertraline, nortriptyline, tranquilizers can be indicated for nervousness and lithium is usually prescribed for pathological stimulation and rigorous temper swings (Office of Communications and Public Liaison Jan 05 2009). Despite their significance in the abolishing HD symptoms, most of these drugs have diverse side effects on patients such as exhaustion, restlessness or hyper excitability.
Current research of Huntington’s disease
The current research of HD has been generated in various areas and they include use of various scientific techniques such as Basic neurobiology. Since the gene that codes for mHTT has been known neurobiologists (who deals with the anatomy, physiology and biochemistry of the nervous system) are studying HD gene and how it causes the ailment. Another technique used is Clinical research where Neurologists, psychologists, psychiatrists, and other investigators are relating the clinical symptoms and sequel of the disease in patients and any developments of new therapeutics. Also Imaging techniques are being used in scientific investigations via PET to identify what the mutant gene does to various structures in the brain in relation to body chemistry and metabolism. Also there has been the use of Animal models (laboratory animals) where the animals are bred to duplicate clinical features of HD and they are helping in learning about symptoms and sequence of the disease. And lastly application of fetal tissue research technique is used whereby fetal tissue in rodents and nonhuman primates to understand, restore or replace functions usually vanished by neuronal degeneration in persons with HD (Office of Communications and Public Liaison Jan 05 2009).
References
- Amanda Krause & Jacquie Greenberg. Genetic testing for Huntington’s disease in South Africa, South Africa medical Journal: Health care Industry, 2008
- Office of Communications and Public Liaison Huntington’s disease: Hope Through research, National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda, MD 20892, 2009
- Oliver Quarrell. Huntington’s disease: Edition: 2, illustrated, London Published by Oxford University Press, 2008, ISBN 0199212015, 9780199212019
- The Huntington’s disease Association, Hunting a cure with care: Neurosupport Centre, Liverpool, L3 8LR (2009).
- University of California-San Francisco, Huntington’s disease (HD): Memory and aging center, California 94117 (2009) Web.