UCL HUNTINGTON’S DISEASE RESEARCH

INFORMATION FOR SCIENTISTS, CLINICIANS, PATIENTS, RELATIVES AND CARERS

UCL HUNTINGTON’S DISEASE RESEARCH

HUNTINGTON’S DISEASE: THE BASICS

What is Huntington’s disease?

Huntington’s disease, or HD, is an inherited or genetic disorder of the central nervous system. It used to be known as Huntington’s chorea. Huntington’s disease usually develops in adulthood and can cause a very wide range of symptoms. The disease affects both men and women.

What are the symptoms?

The symptoms of Huntington’s disease usually develop when people are between 30-50 years old, although they can start much earlier or much later. The symptoms can also differ from person to person, even in the same family.

Sometimes, the symptoms are present for a long time before a diagnosis of Huntington’s disease is made. This is especially true when people are not aware that Huntington’s disease is in their family.

The early symptoms include:

Some people who know they are at risk spend time searching for the first signs that they are developing the disease. They may worry about simple things like dropping a cup, forgetting a name or becoming unusually bad-tempered. Most people do these things occasionally – whether they are at risk from Huntington’s disease or not – so they could be worrying unnecessarily.

Anyone who is concerned should have a word with their GP who may refer them to a neurologist for tests. These tests could include a number of simple assessments and possibly a brain scan. The genetic tests mentioned above may also be used to aid diagnosis.

What happens as HD progresses?

Later on in the illness people experience many different symptoms which may include:

as well as emotional changes resulting in:

Cognitive changes that people experience can result in a loss of drive. Initiative and organisational skills, which may result in the person appearing to be lazy. There also may be difficulty in concentrating on more than one activity at a time.

Sometimes, psychological problems, rather than the physical deterioration, cause more difficulties for both the person with Huntington’s disease and their carers. Some changes are definitely part of the disease process although they made be made worse by other factors. It is depressing to have a serious illness and extremely frustrating not to be able to do things which previously seemed simple.

In the later stages of the disease, full nursing care will be needed. Secondary illnesses, such as pneumonia, are often the actual cause of death.

What causes HD?

HD is caused by a mutation in a person’s DNA. Your DNA is basically lots of instructions for building your body and keeping it running. DNA is organized into individual ‘recipes’ called genes. Each gene is a recipe for one protein (a molecular machine). A mutation in a gene is like a spelling mistake. Some spelling mistakes are harmless, but some result in proteins that don’t work properly or are harmful.

The mutation that causes HD was mapped to a specific gene in 1993 — this gene is now called the ‘huntingtin’ gene, and is abbreviated as ‘HTT’ or ‘HD’ or ‘IT15’. Knowing the location and nature of the HD mutation has allowed people to be tested for the HD mutation since 1993.

So what’s all this about ‘CAG’?

Everyone with HD has the same basic type of mutation. It is an expansion of a normal repetitive piece of DNA on chromosome number 4. Chromosomes are long pieces of DNA which are chains of millions of ‘bases’. Each base is like letters of the alphabet spelling a word. Every base is one of 4 chemicals (adenine, cytosine, guanine, thymine). These bases are abbreviated as A, C, G or T.

Near the beginning of everyone’s HD gene is a repetitive stretch of three letters — CAG. In people without HD, these three bases are repeated fewer than 35 times — usually about 17 times. People with 36 or greater repeats of CAG will develop HD if they live long enough.

Traditionally, CAG is pronounced as three separate letters (‘see-ay-gee’) rather than as a word.

Each person whose parent has Huntington’s disease is born with a 50-50 chance of inheriting the faulty gene. Anyone who inherits the faulty gene will, at some stage, develop the disease.

A genetic test is available from specialist clinics throughout the country. This test will usually be able to show whether someone has inherited the faulty gene, but it will not indicate the age at which they will develop the disease.

How does an expanded CAG repeat cause Huntington’s disease?

Proteins are made from building blocks called amino acids. The three-base sequence CAG in a gene is an instruction to add an amino acid called glutamine to a growing protein. How ever many CAG repeats there are in a huntingtin gene, is how many glutamines will be in the finished protein. So, for example, people with 42 CAG repeats produce a huntingtin protein with 42 glutamine blocks at the start.

Scientists have abbreviations for the different amino acids. Glutamine is abbreviated as ‘Q’, so Huntingtin’s disease is sometimes called a ‘polyglutamine disease’ or a ‘polyQ disease’.

When the huntingtin protein contains too many glutamine blocks, it has a different shape from the normal protein, and behaves differently too. These differences cause the abnormal protein to become harmful to cells, and it’s this harmful behaviour that causes cells to malfunction and die.

Malfunctioning and dying neurons (brain cells), and other cells, are what causes the symptoms of HD.

Can you tell when someone will experience symptoms of HD?

If we look at thousands of HD patients, we find that on average, people with longer CAG-repeat lengths tend to have an earlier age of onset of HD symptoms. At the extreme, people with very long repeats have a severe form of HD with childhood onset. This is often called ‘juvenile HD’ or ‘jHD’. HD patients with adult onset have CAG repeat counts that are lower than juvenile HD patients. The average repeat length in HD patients is about 44.

It’s important to note that the ability to predict age of onset from CAG-repeat length is not at all accurate. Two people with the same CAG repeat length might start to experience symptoms at very different ages — many years or decades different. Because of this, CAG-repeat lengths are useful for scientific and medical research, but aren’t very informative for most people trying to predict their own expected age of onset.

Are there any treatments or cures?

Unfortunately, no treatment or drug has ever been shown to delay or prevent symptoms of HD in humans.

However, there are lots of treatments that can help many of the symptoms of HD, and different people may benefit from different treatments.

Portions of this page were supplied by HDBuzz.net and the Huntington’s Disease Association.

Updated October 13, 2011