Huntington disease is a hereditary disease that causes the degeneration of nerve cells in the brain. Huntington disease, or hereditary chorea, has an extensive impact on a person’s functional abilities and usually results in movement, perceptive and psychiatric disorders (Walker, 2007). It is named after the American physician George Huntington, who provided one of the first descriptions of the disease in 1872 (Huntington, 1872). The disease causes nerve cells in the brain to die which results in progressive difficulties with movement, mood and mental function (Walker, 2007).
Most people with Huntington’s disease develop signs and symptoms in their 40s or 50s, but the appearance of the disease may be earlier or later in life (Walker, 2007). In rare cases, children can also develop Huntington’s disease. It affects both men and women and one of about every 10,000 people has the disease. About 16 percent of cases involve children. In the United States, at any given time about 30,000 have the disease (Neurology Channel, 2009). When the disease begins before the age of 20, the condition is called juvenile Huntington’s disease (Walker, 2007).
Earlier onset often results in a different appearance of the symptoms and a faster disease progression. Medications are available to help manage the symptoms of Huntington’s disease, but treatments can’t prevent the physical, mental and behavioral deterioration associated with the disorder (Neurology Channel, 2009). Symptoms and causes The symptoms of Huntington disease can differ between people. Symptoms deteriorate slowly and the rate of decline depends on the number of brain cells that have died. Death occurs between 10 and 30 years after the first symptoms develop.
The symptoms worsen more quickly in children and death may occur within 10 years (Neurology Channel, 2009). The early symptoms of Huntington’s disease often include: Personality changes including irritability, anger, depression, or a loss of interest. As well as decreased mental ability such as problems making decisions, learning new information, answering questions and remembering important information. Mild balance problems, Clumsiness, and Involuntary movements of the face such as frowning or pouting are also some of the common symptoms (Walker, 2007).
Other symptoms that appear later on are: involuntary movements called chorea, problems with balance and coordination, rapid eye movements, Hesitant or indistinct speech, Problems with swallowing, and loss of mental function called Dementia (Walker, 2007).. Children with Huntington’s disease may have different symptoms that are similar to Parkinson’s disease including rigid muscles, tremors and slow movements. They may also have seizures (Neurology Channel, 2009). Some people may develop psychiatric difficulties such as bipolar disorder or known as manic-depression (Neurology Channel, 2009).
They may have delusions, hallucinations or being paranoid (Neurology Channel, 2009). The cause of Huntington’s disease is by an inherited defect in a single gene (NCBI, 1998). It is an autosomal dominant disorder, which means that a person needs only one copy of the defective gene to develop the disorder (NCBI, 1998). With the exception of genes on the sex chromosomes, a person inherits two copies of every gene; one copy from each parent. A parent with a defective Huntington gene could pass along the defective copy of the gene or the healthy copy.
Therefore, each child in the family has a 50% chance of inheriting the gene that causes this disorder (NCBI, 1998). Genetics All humans have the Huntingtin gene (”HTT”), which provides the genetic code to produce the protein huntingtin (HTT) (NCBI, 1998). This gene has a unique genetic sequence for CAG (cytosine-adenine-guanine) and codes for the amino acid glutamine, a building block for the huntingtin protein (NCBI, 1998). Healthy individuals have this sequence duplicated from 11 to 40 times in their genetic coding without having symptoms of HD (NHGRP, 2009).
However, individuals with the disease have from 40 up to 100 repeated CAG segments (NHGRP, 2009). Juvenile Huntington’s disease occurs with 60 or more repeats, linking the longer chains of CAG sequences to earlier and more aggressive inception of the disease (NHGRP, 2009). Part of this gene is a repeated section called a trinucleotide repeat, which varies in length between individuals and may change length between generations (Walker, 2007). When the length of this repeated section reaches a certain edge, it produces a transformed form of the protein, called mutant huntingtin protein (mHTT) (Walker, 2007).
The conflicting functions of these proteins are the cause of uncontrolled changes which in turn cause the disease symptoms. The Huntington’s disease mutation is genetically dominant, because either of the parents’ HTT genes being mutated causes the disease. It is not inherited according to gender, but the length of the repeated section of the gene. However, the severity of the disorder can be influenced by the gender of the affected parent (Walker, 2007). HD is one of several trinucleotide repeat disorders which are caused by the length of a repeated section of a gene exceeding a normal range (Walker, 2007).
The ”HTT” gene is located on the short arm of chromosome 4 (NCBI, 1998). Arrangement of the trinucleotide repeat depends on the number of CAG with very large repeat counts, which is why HD can occur under the age of 20 (Walker, 2007). Trinucleotide CAG repeats more than 28 which are unstable during replication which increases with the number of repeats present (Walker, 2007). It is rare for Huntington’s disease to be caused by a new mutation, where neither parent has over 36 CAG repeats (Walker, 2007). The basal ganglia, the part of the brain affected by HD, play a key role in movement and behavior control.
Their functions are not fully understood, but current theories propose that they are part of the cognitive executive system (Walker, 2007). Diagnosis and treatment Huntington’s disease diagnosis takes several steps. These steps include: A physical exam, questions concerning personal and family medical history, questions about emotional or mental changes (NHGRP, 2009). If the doctor believes Huntington’s is a possibility, the following tests may follow: psychiatric exam, genetic testing of blood, CT scan, MRI and or EEG (NHGRP, 2009).
The CT scan and MRI tests find changes in brain structure and rule out other disorders. A positive result is not considered a diagnosis, since it may be obtained decades before the symptoms begin. However, a negative test means that the individual does not carry the expanded copy of the gene and will not develop HD (Neurology Channel, 2009). Although there is no cure for this disorder, there are treatments for some of the symptoms. For involuntary movements, a person with HD is likely to be prescribed a neuroleptic such as Tetrabenazine, Reserpine, Trilaton, or Haldol (Neurology Channel, 2009).
For depression, Fluoxetine, Sertraline Hydrochloride, or Nortriptyline is commonly used. Also, tranquilizers can be used to treat anxiety, and Lithium can be used for persons with severe mood swings (Neurology Channel, 2009). Speech therapy can also improve speech and swallowing. It is important that a person diagnosed with HD maintains a high calorie diet, not only to prevent weight loss, but it has also been shown to improve on involuntary movement and behavioral problems (Neurology Channel, 2009).
Scientists are looking at ways to improve the progression of the disease. They are studying certain cancer and AIDS drugs in relationship to HD. They are also looking at the use of stem cells to repair brain cells. Recently, they began testing of a new drug called ACR16 to improve muscle control and brain function (Neurology Channel, 2009). References 1. Huntington G. 1872. “On Chorea”. Medical and Surgical Reporter of Philadelphia. The Hague: Nijhoff. 26 2. National Center for Biotechnology Information (US).
Genes and Disease. Bethesda (MD): National Center for Biotechnology Information (US); 1998-. Huntington disease. http://www. ncbi. nlm. nih. gov/books/NBK22226/ 3. National Human Genome Research Project. 2009. Learning About Huntington’s Disease. http://www. genome. gov/10001215 4. Neurology Channel. 2009. Huntington’s Disease: Overview, Incidence and Prevalence. http://www. neurologychannel. com/huntingtons/index. shtml 5. Walker FO. 2007. “Huntington’s disease”. Lancet 369 (9557): 218–28.