Providing Services for Huntington's Disease Families in Communities Throughout Oklahoma
Huntington's disease (HD), formerly known as "Huntington's chorea", is a fatal hereditary disorder of the brain in which the nerve cells responsible for movement, personality, and behavior slowly degenerate. HD typically begins in mid-life, between the ages of 30 and 45, however, a juvenile form of the disease also exists. Initially the individual experiences psychiatric and cognitive deficits, such as memory loss, apathy, depression, and irritability. As the disease steadily worsens over the next 15-20 years, the affected individual gradually loses the ability for coordinate movement, eventually losing the power to think, talk and reason. Because the patient eventually becomes totally incapacitated and wholly dependent upon others for his or her care, HD profoundly affects the lives of the entire family: emotionally, socially and economically. Unfortunately, at present there is no effective treatment or cure.
Named after Dr. George Huntington, who first recognized the disorder in 1872, HD is one of the more common genetic disorders of man. More than a quarter of a million Americans have HD or are at risk of inheriting the disease from an affected parent. In North America and Western Europe, the prevalence of HD is about 1 affected individual for every 20,000 population. That means there are at least 150 affected individuals in Oklahoma and about 15,000 in the United States. The prevalence is lower in Asians and African-Americans.
The gene responsible for this disorder was identified in 1993 by an international consortium of scientists whose research was supported in part by the efforts of volunteers and contributors to the Huntington's Disease Society of America. The diseased gene, which is found on chromosome 4, acts in a dominant fashion in that one copy of the diseased form of the gene is sufficient to produce disease conditions. Therefore, individuals with one copy of the gene are destined to develop disease symptoms if they live a normal life span. Rarely individuals with HD are found to have two copes of the diseased gene, one copy inherited from each affected parent, but these individuals are clinically indistinguishable from individuals with only one copy of the diseased gene. This observation argues that the normal HD gene does not help delay progress of disease symptoms and that two copies of the diseased gene are no more damaging than a single copy. Sadly, because most cases of HD occur in middle age, the defective gene is often passed on to the children before the parent is aware of his or her disorder.
The error in the Huntington's gene (sometimes also referred to as the IT15 gene) lies in an area called the “CAG” repeat region where the genetic code letters C (cytosine), A (adenine), and G (guanine) are repeated sequentially many times over. For some as yet unknown reason, this repeat segment region expands in patients with HD. In the normal gene, there are 26 or fewer CAG repeats, the intermediate range is 27 to 41, while the mutant version of the gene contains 42 to more than 100 repeats. The number of repeats in the HD gene can increase or decrease with each generation but larger sized repeat regions tend to be most unstable. The severity of the disease also appears to be directly correlated with the number of repeats; the more repeats the greater the severity and earlier the onset of the disease. The longest expanded CAG repeat lengths (>55) give rise to juvenile HD and the shortest (35-39) tend not to trigger disease until very late in life.
The HD gene produces a protein called “huntingtin” that is more than 3140 amino acids long. The variable-sized CAG repeat segment in the HD gene is reflected in the huntingtin protein by a variably-sized region or “polyglutamine expansion”. The extra CAG repeats in the gene code for extra glutamines at one end of the protein, so the mutant form of huntingtin is longer than its normal counterpart. We all have huntingtin in virtually all of our cells but researchers don't know what huntingtin does in the body, nor do they know why the expanded version of the protein that causes HD can lead to death of only certain types of brain cells.
The discovery of the gene was a tremendous breakthrough, but the gene is only the first
in a series of biochemical steps that ultimately lead to brain cell death in
people with Huntington's. Researchers are now investigating the other steps to
find out what the gene does and why it behaves differently in people with HD.
The Oklahoma Chapter of the Huntington's Disease Society of America provides care and assistance to those affected by Huntington's disease, educates the public and professionals about Huntington's disease, and helps in the effort to eradicate the disease by supporting and promoting research efforts.
If you would like further information about Huntington's disease or about the services offered by the Oklahoma Chapter of the Huntington's Disease Society of America, please write to:
Huntington' s Disease Society of America