Ataxias: hunting down the genetic causes of these devastating disorders of balance and coordination

Children with ataxia have problems with balance and coordination, which can rob them of their ability to walk and make everyday activities difficult. It is often uncertain exactly what a child’s future holds – sadly for some children their disorder is progressive and life limiting, whereas other children find their condition remains constant throughout life. Dr Andrea Nemeth, of the University of Oxford, is searching for the genetic causes of ataxia, to give families a better understanding of why they’ve been affected and what the future holds for them.

What is the problem and who does it affect?

No-one knows exactly how many children in the UK are suffering from ataxia. It’s thought to be several thousand.^1,2 We do know that ataxia occurs in all age groups – affecting babies, children, teenagers and adults alike.

“Ataxias are actually a group of different disorders, all characterised by loss of balance and coordination,” explains Dr Nemeth. Sadly, ataxias are often progressive. Typically, children slowly lose their ability to walk, and may eventually need to use a wheelchair, their speech can become slurred and everyday tasks – even just reaching out to have a drink of water – can become difficult.

There is no cure for ataxia, although treatment can relieve some of the symptoms associated with specific conditions.

“Several things can cause ataxia, including infection or illness around the time of birth, tumours, exposure to drugs or genetic factors,” says Dr Nemeth. “However, when a child is first diagnosed, it’s often difficult to find out why they’ve developed the condition.”

All too often, important questions remain unanswered: “If we don’t know what’s causing a child’s ataxia, it’s hard to tell how best to treat him, or her, and difficult to predict whether the illness will progress. This uncertainty causes significant anxiety for children and their families.”

What is the project trying to achieve?

“We strongly suspect that many ataxias are caused by genetic factors, even those previously thought to be non-genetic” explains Dr Nemeth. “Disease-causing changes in around 60 human genes have already been linked to ataxia. However, our research shows many children who have inherited the condition do not have changes in these genes. So we are looking for disease-causing changes in other genes and trying to find out how they work. We will initially investigate 20 families, but aim to increase this number as more families are referred to us.”

If successful, Dr Nemeth’s work could lead to a range of benefits. “We hope that our research will lead to new genetic tests for ataxia, which could spare children from going through more traumatic tests, such as lumbar punctures and MRI scans. It could mean children receive a definitive diagnosis much earlier, along with important information about their outlook for the future. One day, our work might also lead to better treatments.”

What are the researchers’ credentials?

Dr Nemeth’s determination to improve the lives of people with ataxias stems from early experiences treating children whose condition remained unexplained. Nearly twenty years down the line, she has gathered a large collection of DNA samples from children with ataxia and has already identified one new genetic cause of the condition.

References

1. Millie Mae’s World. Raising awareness and funds for Ataxia UK with smiles. 2020Vision – aiming for a cure for ataxia. How many people have ataxia? http://milliemaesworld.co.uk/millie/category/latest-ataxia-news/ Website accessed 12 October 2012.
2. Anheim M et al. Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management. Neurogenetics 2010; 11(1): 1-12.