Genetic Diseases - Huntington's Disease

Huntington's disease (HD), or Huntington's chorea, is an inherited, progressive brain disorder. It causes the degeneration of cells in the basal ganglia, a pair of nerve clusters deep in the brain that affect both the body and the mind. HD is caused by a single dominant gene that affects both men and women of all races and ethnic groups. It does not usually strike until mid-adulthood, although there is a juvenile form that can affect children and adolescents. Early symptoms, such as forgetfulness, a lack of muscle coordination, or a loss of balance, often are ignored. The disease gradually takes its toll over a ten-to twenty-five-year period.

Within a few years, characteristic involuntary jerking (chorea) of the body, limbs, and facial muscles appears. As HD progresses, speech becomes slurred and swallowing becomes difficult. The patients' cognitive abilities decline, and there are distinct personality changes—depression and withdrawal, sometimes countered with euphoria. Eventually, nearly all patients must be institutionalized, and they usually die as a result of choking or infections.

There is no cure for HD. A number of medications may be prescribed to help control emotional and movement problems associated with HD, but the course of the disease cannot be stopped.

Prevalence of Huntington's Disease

HD, once considered rare, now is recognized as one of the more common hereditary diseases. According to the National Institute of Neurological Disorders and Stroke, HD is known to affect about 30,000 Americans; another 150,000 are at a 50 percent risk of inheriting it from an affected parent. Estimates of its prevalence are about one in every 10,000 people.

Prediction Test

In 1983 researchers identified a DNA marker that made it possible to offer a test to determine, before symptoms appear, whether an individual has inherited the HD gene. In some cases, it is even possible to make a prenatal diagnosis on an unborn child. Many people, however, prefer not to know whether they carry the defective gene.

Some individuals choose to be tested because they feel the results will enable them to make more informed decisions about the future—including education, marriage, and childbearing. Those who choose not to take the test may prefer to forego whatever emotional consequences—along with possible losses of jobs or insurance—may incur from the test results. Each choice is highly individual.

A testing center at Johns Hopkins Hospital in Maryland reported that a high proportion of the people who come in for testing find out that they are not carrying the gene. Of the people who do not choose to be tested, the center's physicians believe that many may already have very mild symptoms and suspect that they have the disease.

Gene Responsible for Huntington's Disease Found

In 1993 an international team of scientists from the United States and the United Kingdom announced that after ten years of research, it had discovered the gene responsible for HD. In the HD gene, the mutation involves a triplet of genetic subunits, or bases, known by the chemical initials CAG. In people who do not have HD, the gene has thirty or fewer of these triplets, but patients with HD have forty or more. These increased multiples either destroy the gene's ability to make the necessary protein or cause it to produce a misshapen and malfunctioning protein. Either way, the defect results in the death of brain cells.

The researchers examined seventy-five families with a history of HD and found the abnormal expansion in each case of an afflicted patient. Currently, they are trying to determine if the exact number of excess triplets bears any relation to when in life a person will be affected by the disease. Some scientists fear that the ability to tell people that they are going to develop an incurable disease and pinpoint when they will develop it will make genetic testing, already a difficult decision, even more complicated.

Promising Research Findings

In December 2001 researchers at the University of South Florida reported that fetal tissue—neurons obtained from fetuses—transplanted into the damaged areas of the brains of patients with HD remained disease-free. Earlier in the same year French researchers had reported similar results, confirming that HD did not appear to enter or affect the implanted fetal tissue.

The patients with HD who received the transplants showed measurable improvement in motor and cognitive functions and did not appear to reject the transplanted tissue, leading investigators to speculate that fetal tissue grafts might become the first effective treatment for HD.