Mitochondrial Disease Information Day - Brisbane

More than fifty people gathered in the Auditorium of the Royal Children’s Hospital in Brisbane on Saturday April 10th for the inaugural Information Day on Mitochondrial Disease in Queensland. They were there to listen to a series of experts speak on the disease: its causes, how it manifests, the latest research, and what the future holds. Most of those present were people affected by the disease. Some were carers, and some were supporters there to find out more so that they could make a contribution.

The day was organised by Dr David Coman from the Royal, and he lead off by honouring one of Australia’s foremost researcher into mitochondrial disease, the late Denise Kirby. Dr Kirby had been involved in a host of research programs into metabolic and mitochondrial disorders, and most of those in Australia who were involved in this field had either worked with her or had learned from her work. Dr Coman then introduced the first speaker, Professor Carolyn Sue, Director of the Department of Neurogenetics at the Royal North Shore Hospital in Sydney.

Dr Sue began by describing mitochondrial disease. She went on to discuss how it was diagnosed, what to do if you have it, and the treatments that were being applied by various clinics. Dr Sue said that the prevalence of mitochondrial DNA mutations in persons aged over 50 is one in 250 people but very few of those ‘carriers’ got to hospital as the diagnosis was rare. Mitochondrial DNA was found in the ovum and is usually transmitted maternally (ie through the mother), but most of the genes responsible for the construction, function and maintenance of the respiratory chain are in nuclear DNA which may be transmitted by either parent. Of particular interest to everybody is why the effect on those who carry the mutation is so variable. The severity of the affect is influenced by the percentage of mitochondria in the cells that are malfunctioning, but also nuclear DNA, which is received from both parents, may contribute to disproportionate amounts of abnormal DNA being distributed to the daughter cells as nuclear division proceeds.

Professor Sue then went on to discuss the proposal to set up a national registry of patients. This was vital for the progress of research as it will provide the research institutions with a data base of case histories that will greatly assist them.

Finally Dr Sue discussed briefly some of the treatment regimes that are being tried at her institution and elsewhere. Research is indicating that exercise is very beneficial as it stimulates muscles and may lead to regeneration in some cases. She emphasised that each case has its own characteristics which makes it difficult to make accurate prognoses.

Professor John Christodoulou, Director of the Genetics Program at Westmead Hospital in Sydney followed, and spoke on the treatment of mitochondrial disease in children. Prof Christodoulou said that the main job of the mitochondria is to produce energy as ATP. They mainly burn fats and sugars to do so. Up to 200 properly functioning genes may be needed for the mitochondria to work as they should in producing ATP. Research has shown that there is a vast array of problems associated with mitochondrial dysfunction. The retina and the cochlear have the highest concentrations of mitochondria, followed by the brain, heart, nerves, muscles, kidneys, and others. He emphasised that it is the very complexity of the disease that makes each case different, and which makes it very difficult to know what treatment is appropriate in each case, or to predict what the future might hold.

Some of the methods that are being developed to prevent or treat mitochondrial disease include prenatal testing, gene therapy (removal of faulty genes), regulation of gene activity , attention to improving metabolic function , good and appropriate nutrition, and exercise regimes. He emphasised that all of these therapies and treatments are in their early stages, and a that substantial body of results will be needed before it can be determined with any certainty which will work. He then went on to discuss in detail what was entailed in the various approaches and the reasons behind the decisions to try the various methods.

Professor Christodoulou said that all research was in its early stages. There was little support from government at this stage for testing, except for simple screening blood tests , and what funding there is for specialised testing varies from state to state. There is an urgent need to increase awareness at all levels. Prof Sue would be giving a presentation on mitochondrial disease at a conference of GPs shortly. Governments are being lobbied to increase support. He also indicated that there was a substantial variation in the reliability of mitochondrial test results generated by laboratories across the world, but emphasised that the reference laboratory at the Murdoch Children’s Research Institute in Melbourne was amongst the best in the world

• Dr Jim McGill, Director of Metabolic Medicine at the Royal Children’s Hospital in Brisbane, and a paediatrician, elaborated on the difficulty of diagnosis and predicting prognosis. He spoke on the many tests required to try to confirm a diagnosis of mitochondrial disease. Many of the tests can be normal in an affected person and some of the tests can be positive in non-mitochondrial diseases. The exclusion of other, non-mitochondrial, disorders was therefore an important part of the diagnostic workup.

• Changes in nuclear DNA are a more common cause of mitochondrial disorders in children than changes in mitochondrial DNA. Unfortunately, some genes and even some specific  mutations can lead to different mitochondrial disorders in different individuals. Some mitochondrial disorders may be caused by many different genes. Dr McGill said that 81 nuclear genes had now been identified and it was often necessary to look at many when attempting to confirm the diagnosis of a mitochondrial disorder.

Prenatal testing was still limited to only some disorders. He then discussed the costs that are involved in genetic testing and gene sequencing. Nothing is available from Medicare yet, and individual tests can cost up to $2,000 and more, making diagnosis an expensive process, particularly as many tests are often required.  A review committee is sitting to address Medicare funding and he encouraged those present to make a submission.

In Dr McGill’s opinion what is needed is a series of National Centres of Excellence similar to those that have been set up for other purposes over recent years, with each centre specialising in a particular type of testing. Some laboratories in Australia are of world class but there is a shortage of capacity in some areas which needs remedying.

Following a break for morning tea Dr Doug Lingard, President of the Australian Mitochondrial Disease Foundation, introduced the Foundation. Its main objective is to support the world wide search for a cure for mitochondrial disease. The Foundation’s program includes raising funds to sponsor research, liasing with other similar bodies round the world, getting a national register of patients developed, supporting clinical trials, sponsoring public awareness, lobbying government for changes to legislation and for more recognition of, and financial support for, mitochondrial disease sufferers, and raising support for those who are affected. The Foundation has a web site and plans to distribute a newsletter as well as arranging presentations to bodies such as General Practitioners, Paediatrician's, etc.

Dr Lingard noted that he was frequently asked why an Australian foundation was needed when there were many others in the world. There are many reasons, he explained, the main ones being that donations in Australia were not tax deductible if made to an overseas organization; it was felt that there should be support for Australian researchers and clinicians who were as good as any round the world: and only an Australian organization could lobby Australian governments and develop support groups around the country.

He listed what the Australian Mitochondrial Disease Foundation can do:

• provide information for those who need it;
• maintain a help line;
• support local branches;
• raise awareness;
• provide assistance to those who want to lobby by way of letter templates and advice;
• and advise on support available from such organizations as Centrelink, Self Help groups, physiotherapists, etc.

He drew particular attention to the help line already up and being run single-handedly in NSW by Dr Karen Crawley on her mobile phone. It was hoped to recruit more helpers to give her support.

The activities of the Foundation were then described in more detail by Sean Murray. He described the work on setting up the web site and noted that Information Days were scheduled this year in Sydney, Melbourne, and Perth. There would be the presentation at the GP Conference where 2,000 were expected. Stay-in-Bed-Day, which had been so successful in raising funds in 2009, to the extent that the Foundation had funded 3 PhD students this year, would be on again on August 22nd and everybody was encouraged both to get involved and to publicise the event with all friends. The 2009 event it was estimated had reached 20 million viewers (some more than once) and generated 5,000 hits on Facebook. There had been 99 fund raisers and 2,000 donors. Over $250,000 had been raised to invest in research which had allowed the endowment of the PhD students. He was happy to say that all media time had been donated. The campaign had also been extremely effective in raising awareness of the existence of mitochondrial disease.

He also thought that the theme for the publicity campaign should be designed around ‘Mito what?’ because that was the response that everybody got when they mentioned the disease.

The final session was given over to those on the floor who wanted to make a comment of their own. Some of the themes and issues that arose included:-

• the difficulty of getting doctors to listen to those affected;
• being able to talk to others with the same problems;
• the value of receiving help from doctors, nurses, and friends in getting back their lives;
• keeping going in the face of the problems and getting the motivation to ‘get up in the morning’;
• learning to listen to your body and how to look after it;
• the need for help for carers;
• hearing from others with the same problems and getting advice from their experiences;
• the fact that so many of those affected do not have obvious symptoms so it is difficult to get people to accept that they are afflicted;
• the need for a simple explanation of the disease that could be used when people ask what is wrong;
• the problems and effects of mis-diagnosis; and
• the relief that is felt once help is forthcoming, but the difficulty in asking for it.

One of the speakers advised that a chat site had been set up and that she had found it very helpful.
Dr Lingard wound up proceedings with thanks to the organisers and presenters. He said that he was optimistic that now that there was some serious attention being paid to mitochondrial disease, and with increasing levels of research, it was to be hoped that results would start to flow in the next decade.

The meeting ended with a poster and discussion session followed by lunch. The Foundation offered the opportunity to join and/or donate and AMDF shirts and caps were available for those who wanted them.