A world of genetic research

Kawasaki disease is the only childhood illness to damage the coronary arteries, which can result in long-term health problems.

The death of Jett Travolta, third from left, brought the rare childhood condition known as Kawasaki disease to the attention of the public.

Kawasaki disease, a rare autoimmune illness that mostly affects young children, was in the news recently in two different stories. In the first case, the disease was linked with Jett Travolta, son of the actor John Travolta. Jett died on Jan 2 after he had a seizure. He had apparently been ill for some time and his parents said he had Kawasaki disease. It brought the condition to the attention of the public, and was followed by news of research in Australia into how the disease behaves.

Prof David Burgner from the University of Western Australia co-led a team that studied the entire human genome in an attempt to find new genes involved in making some children more susceptible to the disease. It was first described by Dr Tomisaku Kawasaki in 1967, and although the condition is treatable, little has been learnt since about its causes. It presents itself as an inflammatory condition. It affects several organs including the mucus membranes, the walls of blood vessels and lymph nodes. Its many symptoms include fever, rashes, swollen feet and hands, conjunctivitis and swollen lymph nodes. Children aged six months to five years seem particularly susceptible. It can be fatal, but only one in 1,000 cases result in death. Although it is rare, Prof Burgner explained why it was important to tackle the illness.

"Kawasaki disease is an important and serious illness of preschool children," he said. "Importantly it is the only childhood illness that damages the coronary arteries, in one quarter of untreated children and five to 10 per cent of treated children. This coronary damage may have long-term health implications, including death, angina and heart attacks in childhood and the need for coronary bypass surgery and even, rarely, heart transplant in childhood."

In the research study Prof Burgner's team considered genetic variation among 900 cases of the disease found in children from the US, Singapore, the Netherlands, the UK and Australia. The findings identified genes that may increase the susceptibility of some children to the disease, but further research is needed. "Kawasaki disease is thought to be an abnormal immunological reaction to an unknown infectious trigger. There is a strong genetic component, so genes are important in determining susceptibility, as we believe all children are likely to be exposed to the trigger," Prof Burgner said.

"Our study is the first published that has investigated the entire human genome looking for important associated genes; most studies focus on a few candidate genes. We have identified at least eight new genes that have not previously been described in Kawasaki disease and some of them seem to function together. Some of the genes are involved in cardiovascular health - the function of blood vessels and in control of the immune system."

Identifying eight genes expands the scope of future research considerably. However, studying the entire human genome is not the biggest problem facing the researchers. "The main issue is recruiting enough cases of Kawasaki disease, which is why we embarked on an international study. Ideally we need up to 5,000 cases to cover more of the human genome and find more of the important genes. We were very lucky to work with the Genome Institute of Singapore, who are one of the top genomics facilities in the world - this made the actual genetic laboratory work and analysis possible."

Dr Brian McCrindle, a cardiologist from the Hospital for Sick Children in Toronto, Canada, gave a talk on Kawasaki disease at the Arab Health Congress in Dubai in January. He believes the new findings offer potential for future research. "The research is very preliminary and needs to be verified in other people's work, but there are some promising leads," he said. "Kawasaki disease can look like other diseases and sometimes it doesn't have typical presentation," he said.

Raising awareness is vital because the disease can be misdiagnosed, but developing a cure for any rare disease is difficult. However, Prof Burgner believes the identification of eight new genes will help with the treatment process. "We hope that our work will contribute to the development of a diagnostic test and better treatment within the next few years, but we are not there yet," he said. "At the moment doctors make a clinical diagnosis, based on the rash, fever et cetera, and there is no blood test that really helps. We urgently need a diagnostic test so children are treated earlier and Kawasaki disease is not missed, so reducing the long-term heart problems."

Finding a cure remains a possibility, though. "In Japan, for example, where one in 150 children suffer KD, it may be realistic to develop a vaccine, especially if Kawasaki disease increases the risk of atherosclerosis in later life - this is an unknown area at present," Prof Burgner said. He also believes that the method used in his research of analysing the entire human genome will be adopted as the way forward in studying other infectious diseases.

"Genes are known to be important in determining susceptibility to infection so it is a proven and exciting method to try and identify the important genes that make people more or less likely to get infection and once they have it, more or less likely to survive. This should lead to better prevention and treatment. I suspect tuberculosis, HIV, hepatitis B and C and malaria will be the likely diseases that we will see these sorts of studies in very soon," he said.

For the moment, however, Prof Burgner is keen to continue to develop the research path he is pursuing with Kawasaki disease. There is also the possibility of collaborating with medical professionals in the Middle East. "We are expanding the collaborative genetics group to include Asian and other populations, aiming to work together as a scientific community to crack this mysterious disease. We would very much like to hear from anyone in your region who has an interest in Kawasaki disease and sees many patients," he said.

Peter Donnelly is a science correspondent for the life science division at IIR Middle East