Code breakers | Action Medical Research

Touching Lives - March 2005

Code breakers

Some people have a genetic fault similar to a time bomb ticking away inside their bodies. They know they carry the fault, but they don’t know when, or even if, illness might strike.

Huntington’s disease is such a phenomenon. It is a degenerative brain disorder, but the faulty gene that causes it often has no obvious effect until middle age. Huntington’s slowly diminishes a person’s ability to walk, think, talk and reason and eventually, sufferers become dependent on others for their day-to-day care. There is no cure at present.

Though it was first identified in Victorian times, little is known about why some people who carry the rogue gene develop Huntington’s symptoms in their thirties, whilst others develop symptoms in their fifties, and some, very occasionally, do not suffer the effects of the disease at all.

A groundbreaking two-year Action Medical Research project looking at the genetic faults that cause Huntington’s disease has made real strides in helping doctors to predict the chance of someone developing the condition, and most importantly, when they may become affected.

Bigger gene

Huntington’s disease is an inherited genetic condition — anybody with an affected parent has on average a 50-50 chance of developing the disease — and the faulty gene was identified in 1993.

In simple terms, the Huntington’s gene is ‘bigger’ than normal, because its base code is repeated several times. Scientists have discovered that anyone with over 36 of these ‘repeated pairs’ of code may get Huntington’s disease, but ^no-one could predict at what age the symptoms might begin.^

Generally speaking, the larger the size of the gene, the earlier the age of onset, but this alone is not helpful for predicting an individual’s likelihood of developing the disease because other genetic and non-genetic factors are involved. Soon after the discovery of the gene it was clear that some people with very small enlargements of the gene do not develop symptoms at all — but can still pass on the condition to their children.

Surprisingly common

We now know that Huntington’s is one of the more common genetic disorders that can be inherited from a parent. It affects as many people as conditions such as haemophilia or cystic fibrosis.

Symptoms typically begin in mid-life and progress without remission for ten to 25 years. The onset of Huntington’s disease may occur as early as the age of two, and ^children who develop the juvenile form of the disease rarely live to adulthood.^ The condition affects men and women equally and crosses all ethnic boundaries.

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

The disease affects different people in different ways, but symptoms include involuntary muscular movements leading to uncontrollable jerking of the limbs, body and face; stumbling and clumsiness; lack of concentration; short-term memory lapses; depression; and changes of mood, sometimes including aggressive or antisocial behaviour.

Not surprisingly, many of these symptoms can cause great strain within a family. The time before a diagnosis is made can be very confusing and frightening because people do not understand what is happening to them. For people who know that Huntington’s is carried in their family, a test is available to show whether they have the faulty gene or not.

But the test cannot predict when symptoms will begin, so some people ‘at risk’ elect not to take it and for many others, simply not knowing when symptoms may arise can cause huge anxiety.

The study

The Action Medical Research-funded study involved collecting DNA samples from 200 Huntington’s sufferers from around the world, and now the team — led by Dr Oliver Quarrell at Sheffield Children’s Hospital — has a much clearer idea of the likely age of onset for people with very small gene enlargements.

It’s the largest study of its kind, and gives clinicians and researchers access to large amounts of data to help unravel the mysteries of Huntington’s and why it affects different people at different stages in their lives.

Dr Quarrell told Touching Lives,”We are very grateful to Action Medical Research for funding this study — without it the work simply could not have happened.We concentrated on a group of people with between 36 and 39 repeats in their genetic code. In other words, people who fell into the grey area that may or may not develop symptoms of Huntington’s disease.

^”The results we now have help us determine the probability of a person developing Huntington’s by a specific age^, which means doctors will be able to give patients much better information on the likelihood of their developing the disease.”

Finding answers

“So much is still unknown about Huntington’s. We know for example that other genetic factors can contribute to its onset, but we do not know what they are. So the information from our project will be made available to the wider scientific community in the hope that it can help to answer some of these questions.”

The team at Sheffield worked with researchers at the Western General Hospital in Edinburgh to study the genetic sequences and carefully check each result. All 200 samples were taken from anonymous donors across the UK and as far afield as Australia.

Dr Quarrell was joined in the study by Dr Ann Dalton, Mr Alan Rigby and Dr Jonathan Warner. He said,”We now have much better quality information on likely age of onset than ever before, which is vital in a disease for which there is still no cure.”

Interesting history

The condition is named after Dr. George Huntington, a physician from Long Island, New York, who first described the disorder in a paper he wrote in 1872 aged just 22. George came from a long line of medical doctors, and since childhood had accompanied his father on his rounds as they visited Long Island families afflicted by this ‘rare but terrible disease’.

In his paper, George referred to the condition as a ‘chorea’, which in Latin and Greek means ‘chorus’ or ‘a group of dances’. This was the term given to what were known as the many ‘dancing disorders’ that came to notice in the Middle Ages, characterised by jerking and involuntary movement. And so ^the condition we now know as Huntington’s disease went by the name of Huntington’s Chorea for many years.^

Its essential features, Dr Huntington noted, included a ‘hereditary nature’, a ‘tendency toward insanity’ and ‘manifestation as a grave disease in adult life’. He also commented on the abnormal movements caused by the disorder and the lack of knowledge of its cause and any possible cure.

Interestingly, because he had only encountered the condition in the Long Island patients he had visited with his father, Dr Huntington suggested in his report that it might be confined solely to those families, and could therefore be considered ‘merely as a medical curiosity.’ Nowadays of course, with the benefit of subsequent research, we know just how widespread and common it is.

Music legend

The legendary singer and songwriter Woody Guthrie suffered from Huntington’s disease, which caused his gradual physical and mental decline in the years leading up to his death in 1967.

When symptoms started to show in the early 1950s, they were wrongly attributed to alcohol or schizophrenia, and it took a long time to get an accurate diagnosis, even though his mother had shown similar symptoms and had been institutionalised 30 years before. It was gradually realised that she had passed Huntington’s to her son.

The condition robbed Woody Guthrie of his health and musical ability over the course of 20 years, and towards the end took his power of speech and confined him to a wheelchair.

The Woody Guthrie Foundation, set up in 1972, preserves his folk and country music legacy. For more information visit — the site details Woody’s illness, which he sometimes described through his lyrics and poetry. Woody’s wife Marjorie was the founder of the Huntington’s Disease Society in America.

Westfield Health Scheme and W J Underwood’s Charitable Trust for Medical Research kindly donated to this project.

Help us spread the word