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 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 , 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 , 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 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 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.
