The Mito Foundation has co-funded with the Australian Genomic Health Alliance (AGHA) an ongoing groundbreaking genomics study to improve mitochondrial disease (mito) diagnosis.

The mito diagnostic odyssey doesn’t have to be long, painful or inconclusive. The Mito Foundation is working each day to empower people living with undiagnosed mito to find a diagnosis and enable the best treatments possible.  Ultimately, this the Mito Foundation co-funded project will increase diagnosis rates, shorten the diagnostic odysseys, and improve quality of life for Australians with undiagnosed mito.

If you or your doctor suspect you may have mito, click here to learn more about getting involved.

Most people with mito undergo months, if not years, of painful and invasive tests and are often misdiagnosed, enduring unnecessary anguish and stress. However, the Mito Foundation has funded a project to significantly improve the mito diagnosis pathway. This large project tests out a revolutionary genetic technology, whole-genome sequencing, which is able to diagnose mito by analysing a person’s entire genetic code. The Mito Foundation, in partnership with the Australian Genomic Health Alliance (AGHA), has provided funding to ensure that every Australian with undiagnosed mito will have access to a genetic diagnosis.

Sean Murray

“The Mito Foundation got on board with this project because diagnosis is a critical issue for people with mitochondrial disease. A huge number of patients have clinical symptoms but no definitive diagnosis, and many patients undergo a difficult diagnostic odyssey.”  –  Mito Foundation CEO, Sean Murray

Whole-Genome and Whole-Exome Sequencing for Mito

This study evaluates two new types of genomic sequencing, whole-genome and whole-exome sequencing. Both methods analyse far more genes than standard genetic tests, which only scan for known mito genes, missing hundreds of possible locations where the disease may originate. Both only require a minimally invasive blood draw, far less painful than the standard muscle biopsy. Whole-genome sequencing analyses a person’s entire genetic code. This is an immense amount of data, consisting of over 3 billion individual parts. Whole-exome sequencing only analyses the genes that code for proteins. This is around 1 percent of a person’s genetic code. Because all known mito arises from misformed or missing proteins, most experts agree that whole-exome sequencing is sufficient to diagnose the disease. However, this study will collect critical data to compare the two forms of sequencing.

Genomic sequencing is the latest advancement in diagnostic medicine, and Australian mito patients are among the first to benefit from it. Experts believe that mito diagnosis requires the type of in-depth screening that genomic sequencing offers. This is because there are many genes that cause mito (the latest estimate is 1500), and only 250 of these are known to scientists. Therefore, mito requires a broad search to identify its genetic origin.

Figure 1: A scientist examines a DNA microarray. This is a colourful way of representing genetic information in great detail. Each colour represents a tiny fragment of the genetic code. It only takes one missing or altered genetic fragment to cause mito


Study Overview

The study is led by two mito experts, paediatric geneticist John Christodoulou and research professor David Thorburn. Both are chairs of genomic medicine at Murdoch Children’s Research Institute in Melbourne. Their lab has already begun to sequence samples for this project, which is set to last two years and include over 210 children and adults from each state in Australia. Patients will be seen at 13 major referral centres across the country. After an initial evaluation to rule out other aetiologies, patients will have their blood drawn and submitted for genomic sequencing. Half of the samples receive whole-genome sequencing, the other half receive whole-exome sequencing. These results will be read and interpreted by medical geneticists, doctors who are experts in analysing genetic code. It will take about three months to sequence and analyse the results, and patients will be informed as soon as the results are available.

Significance of Genomic Sequencing for Mito Patients

The long-term impact of this study is expected to be significant. Researchers are gathering information about cost, effectiveness, and patient satisfaction, and building evidence to convince the Australian government that genomic sequencing should be standard for mito diagnosis. This study is also expected to discover new mito genes, and expand scientific knowledge about the cause of mito, building evidence toward new treatment or a cure. The goal is to implement genomic sequencing early in the diagnostic journey for mito.


“We are hoping to help patients avoid the traditional invasive diagnostic pathway for mitochondrial disease. This usually involves a muscle biopsy and MRI scan under a general anaesthetic which increases the risk of complications for patients with mito, especially for children.”   – Professor John Christdoulou, Project Leader

For people living with mito, the benefits of a genetic diagnosis extend to many aspects of health and individual well-being. A genetic diagnosis enables doctors to begin appropriate treatment and coordinate care. A genetic diagnosis reveals the disease’s inheritance pattern, which is crucial to reproductive decision making. A genetic diagnosis opens doors to National Disability Insurance Scheme (NDIS) funding and enables participation in clinical trials for new treatments.  As much of the mito community is aware, a genetic diagnosis brings closure to the diagnostic odyssey; it provides the emotional relief of understanding the basis for one’s symptoms.

This project is funded by the generous support of numerous corporate grants as well as a dedicated community of the Mito Foundation supporters. To support this and similar projects, click here.

If you or your doctor suspect you may have mito, follow this link to learn more about becoming involved in this study.

Study Update

From March 11 2019, Dr Shanti Balasubramaniam has taken over from Carolyn Ellaway as the Sydney Children’s Hospital Network (SCHN) clinical lead for the Australian Genomics mitochondrial flagship. The Flagship has successfully established 11 clinical sites, with the majority now actively engaging participants. As of February 2019, 71 children and 46 adults have been recruited for the study.

Professor Christodoulou said, “We’re really pleased to pass this important milestone in the study, where essential infrastructure for the study is in place and participants are moving through to genomic testing. We’re grateful to the Mito Foundation for its continued support and efforts to enable sequencing for our participants.

“We’re also encouraged by the diagnostic rate we’ve seen to date as a result of testing. We hope that by capturing the economics of these testing approaches, we can make a case to government for subsidised access to genomic testing for those with a suspected mitochondrial disorder.”