More than half of people with mitochondrial disease can be diagnosed via genomic sequencing, a finding that will revolutionise care for families, according to a new study. And the Melbourne researchers have discovered what boosts and impacts the testing results, especially among children.

The national study, led by Murdoch Children’s Research Institute (MCRI), found genomic sequencing of blood, a lab test that can help identify genetic causes of health and developmental problems, could speed up and simplify the diagnostic journey, sparing those with suspected mitochondrial disease from invasive testing.

MCRI Dr Alison Compton said the findings were significant for clinical management, allowing families to make informed reproductive decisions and enabling research into new treatments.

Image: Dr Alison Compton

The Australian Genomics Mitochondrial Disorders Flagship, involving clinicians and researchers from around the country, conducted the study to determine the diagnostic impact of genomic sequencing using blood samples from those with mitochondrial disease symptoms.

For the study, 140 children and adults were recruited from NSW, Queensland, South Australia, Victoria, Tasmania and Western Australia. Those enrolled had symptoms including muscle weakness, intellectual disability, developmental delay, seizures and hearing impairment.

Published in Genetics in Medicine, the research reported a high diagnostic yield of 55 per cent, with 71 per cent of diagnoses made in genes known to cause mitochondrial disease.

Mitochondria are like the batteries inside our cells, providing the energy our bodies need to operate. When mitochondria are faulty due to genetic variations in key genes, cells begin to die until eventually, organ systems start failing.

Mitochondrial disease can be inherited through mutations in DNA that specifically affect mitochondrial function. About 50 Australian children are born every year with mitochondrial disease.

“When mitochondria don’t work properly our cells don’t get the energy they need, which can lead to various health issues,” Dr Compton said. Since every part of the body needs energy to work, problems with mitochondria can affect many different organs and systems, but especially those with high energy needs like the brain, heart, muscles and the nervous system.”

MCRI Professor David Thorburn said families living with mitochondrial disease often endured prolonged diagnostic journeys and invasive testing, yet many remain without a diagnosis.

Image: Professor David Thorburn

“A diagnosis is crucial for patients, giving their clinical and allied health teams insights into prognosis and often allowing families to make informed reproductive decisions,” he said. However, the complexity and variability of the underlying causes of mitochondrial disease have made them hard to accurately diagnose.

“Often families with mitochondrial disease have visited multiple specialists, been misdiagnosed several times or required extensive evaluations, including invasive biopsies.”

The study found diagnostic rates were much higher among children than adults, at 71 per cent and 31 per cent respectively. The research noted mitochondrial DNA genetic variations in adult blood can decline with age, even becoming undetectable, which could be a contributing factor to the lower detection rate. 

Additionally for children, higher Modified Nijmegen scores, a criteria tool to evaluate the likelihood of a child having mitochondrial disease, correlated with increased diagnostic yield.

The testing also showed that almost a third of diagnoses were made in genes not known to cause mitochondrial disease.

“The findings emphasise the clinical variability and overlap of mitochondrial disease with other inherited disorders,” MCRI Professor John Christodoulou said. It demonstrates the value of genomic testing by providing important health information that can lead to a diagnosis, more appropriate treatment or identify further health risks.”

Leigh and Laura’s son Tyler, 15, was diagnosed with mitochondrial disease four years ago. After years of testing, Tyler was eventually diagnosed via genomic sequencing.

Image: Tyler was diagnosed with mitochondrial disease via genomic sequencing

Read more about Tyler’s diagnostic experience and how the condition impacts his life.

The treatment for mitochondrial disease focuses on managing symptoms and supporting overall health.

However, The mitoHOPE program, established in 2023, is offering hope to hundreds of families affected by some forms of mitochondrial disease. The pilot program, led by Monash University in collaboration with MCRI and other partners, aims to determine the safety, efficacy and feasibility of using mitochondrial donation in Australia.

Under the program, assisted reproductive technology will be harnessed and involves the nuclear DNA, the genetic material found within the nucleus of a cell, from an intending parent’s egg being transferred to a donor egg with healthy mitochondrial DNA. The child would inherit nuclear DNA from the intending parent/s and mitochondrial DNA from the egg donor.

The project aims to assist women to have genetically-related children who may not inherit the predisposition to some forms of mitochondrial disease and will help determine the best way to offer mitochondrial donation to women with the disease.

Publication: Rocio Rius, Alison G. Compton, Naomi L. Baker, Shanti Balasubramaniam, Stephanie Best, Kaustuv Bhattacharya, Kirsten Boggs, Tiffany Boughtwood, Jeffrey Braithwaite, Drago Bratkovic, Alessandra Bray, Marie-Jo Brion, Jo Burke, Sarah Casauria, Belinda Chong, David Coman, Shannon Cowie, Mark Cowley, Michelle G. de Silva, Martin B. Delatycki, Samantha Edwards, Carolyn Ellaway, Michael C. Fahey, Keri Finlay, Janice Fletcher, Leah E. Frajman, Ann E. Frazier, Velimir Gayevskiy, Roula Ghaoui, Himanshu Goel, Ilias Goranitis, Matilda Haas, Daniella H. Hock, Denise Howting, Matilda R. Jackson, Maina P. Kava, Madonna Kemp, Sarah King-Smith, Nicole J. Lake, Phillipa J. Lamont, Joy Lee, Janet C. Long, Mandi MacShane, Evanthia O. Madelli, Ellenore M. Martin, Justine E. Marum, Tessa Mattiske, Jim McGill, Alejandro Metke, Sean Murray, Julie Panetta, Liza K. Phillips, Michael C.J. Quinn, Michael T. Ryan, Sarah Schenscher, Cas Simons, Nicholas Smith, David A. Stroud, Michel C. Tchan, Melanie Tom, Mathew Wallis, Tyson L. Ware, AnneMarie E. Welch, Christine Wools, You Wu, John Christodoulou and David R. Thorburn. ‘The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses,’ Genetics in Medicine, an official journal of the American College of Medical Genetics and Genomics. DOI: 10.1016/j.gim.2024.101271

*The content of this communication is the sole responsibility of MCRI and does not reflect the views of the NHMRC.

Available for interview

Dr Alison Compton, MCRI Team Leader, Brain and Mitochondrial

Professor David Thorburn, MCRI, Group Leader, Brain and Mitochondrial

Professor John Christodoulou, MCRI Theme Director, Brain and Mitochondrial

Leigh, whose son Tyler, 15, has mitochondrial disease

Media

Murdoch Children's Research Institute
Phone: +61 457 365 848
Email: show email address

About Murdoch Children’s Research Institute

Murdoch Children's Research Institute is the largest child health research institute in Australia committed to making discoveries and developing treatments to improve child and adolescent health in Australia and around the world. They are pioneering new treatments, trialling better vaccines and improving ways of diagnosing and helping sick babies, children and adolescents. It is one of the only research institutes in Australia to offer genetic testing to find answers for families of children with previously undiagnosed conditions.

Funding

The Mitochondrial flagship project was funded by the Australian Genomics Health Alliance (Australian Genomics) NHMRC Targeted Call for Research grant GNT1113531 and supported by NHMRC grants 1164479, 1155244, 1159456, and 2009732, and the US Department of Defense Congressionally Directed Medical Research Programs PR170396. We acknowledge the Australian Mito Foundation and the Crane, Perkins and Miller families for their financial support.