What is Huntington’s disease?

• Huntington’s disease is a rare inherited disorder involving the progressive loss of particular nerve cells in the brain.
• The disease is characterised by dementia of gradually increasing severity leading to the need for full nursing care.
• In 90 per cent of cases the disease symptoms appear between the ages of 30 and 50.
• Huntington’s disease occurs in about one in 15,000 people across the globe.

Genetics

• Huntington’s disease is a single gene disorder caused by a mutation in the HD (also known as HTT) gene on chromosome 4.
• It is an autosomal dominant disease. This means that a single defective gene copy will cause disease.
• Huntington’s disease is caused by a mutation in the HD gene in which the same three bases (CAG) are repeated many more times than normal. This is known as a CAG trinucleotide repeat expansion.
• In people who don’t have Huntington’s disease this section of CAG repeats in the gene is usually only repeated 10 to 35 times.
• In people with Huntington’s disease, this section is repeated over 36 times and can be repeated more than 120 times.

Biology

• The HD gene normally provides instructions for making a protein called huntingtin.
• Huntingtin is found in many tissues in the body, but the highest levels are seen in the brain.
• The exact function of huntingtin is unclear but it is essential during development, especially the development of nerve cells.
• A mutated HD gene has an increased number of CAG repeats at one end. Described by scientists as a repeat expansion, or ‘genetic stutter’.
• This leads to the production of an abnormally long version of the huntingtin protein. This long version is then cut into smaller, toxic fragments that accumulate together and disrupt the normal functions of nerve cells.
• The greater the number of repeats, the earlier the onset of the disease and the more severe the symptoms.

Symptoms

• The average age of onset is 35 to 44 years old.
• There are both physical and psychological symptoms that vary from patient to patient.
• Early physical signs may include:
  • slight, uncontrollable muscular movements
  • clumsiness
  • loss of short-term memory
  • inability to concentrate.
• This may be accompanied by:
  • mood swings
  • depression
  • uncharacteristic aggressive behaviour.
• As the disease progresses, the symptoms become more severe:
  • the involuntary movements become more pronounced
  • the psychological problems worsen
  • the patient may experience weight loss
  • the patient may have difficulties with speech and swallowing.
• Lack of motivation may lead to depression and sometimes even the simplest tasks can seem impossible.
• Full nursing care may eventually be needed.
• Huntington’s disease is inevitably fatal, with an average life expectancy of 20 years after the onset of symptoms.
• Muscular difficulty in clearing the lungs can increase the risk of pneumonia, a common cause of death.

Diagnosis

• Tests for Huntington’s disease are offered to individuals with a history of the disease in the family.
• These will comprise of a neurological examination which will assess:
  • reflexes
  • muscle strength and tone
  • sense of touch
  • vision and hearing
  • coordination and balance
  • mood
  • mental status.
• Then individuals are often referred for a psychiatric evaluation to assess:
  • emotional state
  • behaviour
  • evidence of substance abuse
  • coping strategies.
• Then the doctor may ask for tests to examine the brain with:
  • brain-imaging tests (for example, MRI or CT scans)
  • electroencephalogram (if an individual has experienced seizures) can help identify areas of the brain that are not working properly by picking up on the brain’s electrical signals.
• Genetic testing to identify the mutated HD gene is also an option to confirm a diagnosis of Huntington’s disease.
• Predictive genetic tests can be given to someone who has a family history of the disease but currently shows no obvious symptoms.
• Genetic testing is performed with extensive genetic counselling to help individuals come to terms with what the future might hold if they test positive.
• Prenatal tests for Huntington’s disease are also available but there are ethical concerns associated with terminating a pregnancy following a positive result for Huntington’s. This is because an individual may only develop the disease when they are in middle age and could spend the majority of their lives happy and healthy.

Treatment

• There is currently no cure for Huntington’s disease.
• The symptoms can be alleviated in a number of ways to improve quality of life:
  • drugs can be given to prevent involuntary movements and control mood swings and depression
  • speech therapy can be given to improve speech and ease swallowing
  • a well-balanced diet can prevent weight loss and may have a positive impact on other symptoms.