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Huntington’s disease (HD) is a rare genetic disease of the central nervous system. Named after its American discoverer, Dr. George Huntington, Huntington’s disease (HD) is a devastating degenerative brain disorder for which, at present, there is no cure. Huntington’s chorea – derived from the Greek word chorea meaning “dance” – as it came to be known, is a reference to the uncontrollable movement of the head, trunk and limbs, which is often characteristic of the disease. However, this is only one of the clinical features of HD, whose emotional and cognitive symptoms can be equally debilitating. HD can be described according to its genetic basis, diagnosis, symptoms, and treatment.

HD is inherited. After a 10-year search, scientists announced in 1993 that they had found the gene that causes HD. It has been isolated to the short arm of chromosome number four. The mutation – known as a CAG-trinucleotide repeat – encodes for glutamines in the gene for “Huntington.” An estimated 30,000 Americans have Huntington’s disease. Males and females are equally affected, as are all racial and ethnic groups. A further 150,000 people have a 50-50 chance of inheriting the disease from an affected parent and are said to be “at risk.” The main features of this pattern of inheritance include the presence of the condition in every generation, equal frequency and severity of the condition, and the existence of a more severe variety of the disease in individuals inheriting two changed genes, or the “double-dominant” form of the disease. Anyone inheriting the gene will eventually develop the disease. Individuals who do not inherit HD cannot pass it on to their children, and so the chain of inheritance is broken.

The discovery of the gene for this disease offers the prospect of early detection of individuals at risk. A predictive test allows people at risk to learn whether or not they will later develop the disease. This provides families with informed genetic counseling. New tests generally only require a blood sample from the person being tested. Pre- and post-test counseling is a necessary and important part of the testing procedure.

People who have inherited HD begin to exhibit symptoms when they are between the ages of 30 and 45. Although HD may go unnoticed at first because the affected areas of the brain decay gradually, the decay leads to chorea and loss of mental competence and ends in severe dementia (خبل) and death. The symptoms include depression, mood swings, forgetfulness, clumsiness, twitching, and lack of coordination. Sufferers initially develop a tendency to fidget, which, over a period of months and years, progresses into jerky, choreiform movements. These movements, known as chorea, are spasmic in nature, occur without purpose, cannot be controlled, and may be violent. As the disease progresses, the severity of the symptoms increases. Concentration and short-term memory are diminished, and involuntary movements become more pronounced. Walking and everyday activities become difficult, and speech and swallowing abilities deteriorate. Mental problems may progress more slowly than the chorea. The person’s behavior and personality change, and in time the individual becomes utterly dependent on others for support.

Finally, despite there being no known treatment to stop the progression of HD, there are certain pharmacological treatments to reduce chorea and behavioral disturbances. For example, doctors may prescribe the drug haloperidol for symptoms. However, drugs may impair voluntary movement and, consequently, functional capacity. Therefore, drug therapy should be highly individualized and generally restricted to patients with severely disabling symptoms. Both sufferers from the disease and their families are likely to be greatly affected and challenged, emotionally, socially and economically, by the disease.

Recent research efforts into autosomal dominant inherited diseases may ultimately lead to an effective treatment for HD. As previously noted, the location of the gene responsible for HD was discovered in 1993. More recent research efforts have been directed at discovering exactly how the disease destroys brain cells leading to the rapid degeneration of brain tissue. This degeneration results in both physical impairment of motor function (i.e., chorea) and in the degradation of mental function. In August 1997, researchers from Guy’s Hospital in London and the Max Planck Institute in Berlin published two studies in the journal Cell. These studies claim to have uncovered the mechanism whereby HD kills brain cells in human beings. Four years ago, scientists learned that HD results from a mutant gene that produces a bad version of a normal protein. The CAG-trinucleotide repeat causes three units of genetic code to be repeated dozens of times. The more recent discovery is that the protein produced by this gene – a substance known as “Huntington” – clumps together in solid balls of material that collect inside the nuclei of brain cells. Scientists made this discovery by cutting out the repeated part of the gene, inserting it into mice, and watching the results. The animals quickly developed a disease something like HD, and their cells became clogged with clumps of the mutant protein generated by the gene. Scientists at Johns Hopkins University found the human version of this protein in the nuclei of brain cells from HD victims. The next step will be to test existing drugs in tissue culture to see if they either dissolve the protein clumps or stop them from forming in the first place. If the clump-blocking drugs are successful in the test tube, they will be tried in mice with the mutant gene. If tests with mice prove promising, then the next step is human trials.