Patients with serious genetic conditions given fresh hope of diagnosis

Mitochondrial disease is a serious genetic condition that affects the way the body coverts food into energy.  There are over 100 types of mitochondrial disease, and about one child born every week in Australia will develop a severe mitochondrial disorder in their lifetime; about half of them will die in childhood.

Mitochondrial disorders are notoriously difficult to diagnose due to the multitude of genes and the highly variable symptoms across various organs. The current diagnostic process is an extremely invasive and expensive process for patients, and often doesn't result in a definitive diagnosis.

While the next generation sequencing technology has proven successful in uncovering novel disease genes in a research setting, researchers wanted to see whether it could also play a functional role in diagnostics in a clinical setting.

Researchers looked at 42 patients with mitochondrial disorders and sequenced the DNA of the mitochondrial genome, the 100 genes previously linked to mitochondrial disease, and over1000 additional genes that are known to play a role in mitochondrial biology.

The study, which is published in Science Translational Medicine, found that using the technology 25 per cent of cases were immediately diagnosed; and a further 25 per cent of cases will be able to be diagnosed in the next few years as more genes are formally linked to disease.

Lead researcher, Professor David Thorburn, from Murdoch Childrens Research Institute, said the rate of diagnosis was likely to significantly increase in the future and the technology will greatly improve their ability to diagnose some of the most complicated genetic disorders. 

"New 'next generation' DNA sequencing technologies are transforming the way we do research on inherited diseases. However, it remains a real challenge to transfer these approaches from a research tool into methods that can be used efficiently by doctors trying to sort out if a patient's disease is due to a genetic condition," he said. 
 
"Although not successful in every child, this new technology is a big advance that will allow us to speed up diagnosis for families to end their diagnostic odyssey.  It should mean that within the next few years we can diagnose most children with suspected mitochondrial disease within about a month using just a blood sample, instead of needing a muscle biopsy and taking months or years.

"Our approach is also suitable for other complicated genetic conditions like epilepsy, deafness and some forms of heart disease." 

Professor John Christodoulou, Director of the Western Sydney Genetics Program at The Children's Hospital, Westmead, said the study shows how this new technology will be useful for a clinical setting and could eventually make targeted treatments a reality for mitochondrial disease patients. 

"The use of this technology will mean families can finally get off the diagnostic treadmill, which for some families can take years, with all that heartache and uncertainty for the families, and the discomfort for the patient who is subjected to multiple tests," Prof Christodoulou said.

"Hopefully our discoveries will lead other doctors to test their patients with suspected mitochondrial disease. Then, as more individuals with these genetic mutations are identified, we will hopefully get a better correlation between specific mistakes in the genes and the severity of the disease for patients, enabling doctors to be more accurate when discussing prognosis with families.

"It also gives more certainty about the potential genetic risks to other family members and allows them to consider their reproductive options more definitively."

Australian Mitochondrial Disease Foundation (AMDF) president Dr Doug Lingard said the findings represent a huge step forward in transforming the diagnosis of mitochondrial disease, of which there are more than 100 known types.

"Scientists only discovered in 1988 that mutations in mitochondrial DNA caused disease, so it's been a steep learning curve to find and develop effective diagnostic methods," Dr Lingard said.

"This Australian breakthrough shows that combining world-leading research with the latest technology can make a real difference to patients and their families. 

"It's particularly exciting because the AMDF has recently funded priority access at Royal Perth Hospital to one of Australia's first Next-Generation DNA Sequencing facilities, which will enable much faster, cheaper and more accurate diagnoses of mitochondrial disease for Australian patients."

Dr Lingard and his wife Margie lost their seven-year-old son Alex to mitochondrial disease 28 years ago, when knowledge of the disease was scarce. Their daughter Rose also suddenly developed debilitating symptoms several years ago at the age of 20.

"We waited over two decades for Alex's diagnosis, and had an agonising wait of many months for Rose to be diagnosed before doctors could manage her symptoms properly and she could come home from hospital," Dr Lingard said. 

"Having a quick and simple test to diagnose mitochondrial disease would have saved much distress and despair.  However, while diagnosis may provide considerable relief and resolution for patients and their families, there is still no targeted treatment and no cure, so continued research is vital."