Huntington's disease 27/1/04. By Richard Twyman A progressive neurodegenerative disorder that usually strikes in middle to late adult life.

Overview

Huntington's disease is a rare inherited disorder involving the progressive loss of selected nerve cells in the brain. This results in dementia of gradually increasing severity, and eventually requires full nursing care.

In over 90 per cent of cases, the disease symptoms appear between the ages of 30 and 50. Although there is no cure for the disease, early symptoms can be managed with drugs and other forms of therapy to improve quality of life.

Genetics

Huntington's disease is a single gene disorder caused by a malfunctioning gene on chromosome 4. It is an autosomal dominant disease, which means that only one copy of the gene needs to be defective. Indeed, unlike many dominant diseases, the possession of one defective copy of the gene results in disease symptoms that are every bit as bad as those caused by two defective copies.

The occurrence of the disease is about one in 15 000 across much of the world, although the incidence is higher in some specific populations, such as the Lake Maracaibo region of Venezuela.

The disease gene is named HD (for Huntington's disease) and the protein is called huntingtin. The exact function of the huntingtin protein is unclear, but it is known to be associated with microtubules and synaptic vesicles, suggesting a role in the transport of substances or cell components along the microtubules to the synapses (the structures which facilitate communication between neurons). There is also some evidence that huntingtin is involved with apoptosis (deliberately programmed cell death).

The mutation causing the disease is a pathogenic trinucleotide repeat expansion. There is a series of repeats (in this case the sequence CAG) within the coding region of the gene that can expand or contract from generation to generation. This produces huntingtin proteins with variable numbers of glutamine residues. Once the number of repeats exceeds 35, it becomes unstable and can increase rapidly in subsequent generations. The greater the number of repeats, the earlier the onset of the disease and the more severe the symptoms.

Symptoms

Huntington's disease has both physical and psychological symptoms, but the indications vary from patient to patient. The early physical signs of the disease may include slight, uncontrollable muscular movements (chorea), clumsiness, loss of short-term memory and an inability to concentrate. This is often accompanied by mood swings, depression and uncharacteristic aggressive behaviour.

As the disease progresses, the above symptoms become more severe. The involuntary movements become more pronounced, the psychological problems worsen, and the patient may experience weight loss, and difficulties with speech and swallowing. Motivation becomes a problem and depression can set in. Eventually, even the simplest tasks become impossible and full nursing care is required. Huntington's disease is inevitably fatal, although in many cases the actual cause of death is a secondary disease such as pneumonia.

Diagnosis

Tests for Huntington's disease are offered to individuals with a history of the disease in the family, although this must be accompanied by counselling to help such individuals come to terms with the future. A great deal of anxiety can be caused when those living in the shadow of Huntington's disease spend time looking for the symptoms and anticipating their onset. Prenatal tests for Huntington's disease are also available, although the prospect of terminating a pregnancy because the child may develop a disease in middle age raises considerable ethical concerns.

Treatment

There is no cure for Huntington's disease, but the symptoms can be alleviated in a number of ways to improve quality of life. Drugs can be used to prevent the involuntary movements and control the mood swings and depression, while in later stages of the disease speech therapy is useful both to improve speech and facilitate swallowing. A well-balanced diet can prevent weight loss and may also have a positive impact on other symptoms. The average life expectancy of the patient once the disease has been diagnosed is about 15 years.