‘Uphill is an understatement’: Mitochondrial diseases under the microscope

At age 15, Tyler Caulfield is legally blind; he is one of thousands of children suffering from relatively unknown mitochondrial diseases.

Tyler Caulfield, 15, with his father, Leigh, and mother, Laura. Tyler has mitochondrial deletion syndrome.

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Genomic testing provides the best hope of early diagnosis for a persistently devastating variety of diseases most prevalent in children, a new Australian study has found.

Research from the Murdoch Children’s Research Institute indicates that 55 per cent of mitochondrial diseases could be diagnosed via a genetic blood test, a figure that rises to 71 per cent among children.

Mitochondria, the cell organelles responsible for fuelling the body, are prone to genetic variations that can lead to widespread cell death and organ failure. Mutations in DNA affecting mitochondrial function are often heritable.

Most significantly, the MCRI was able to determine what factors could increase the diagnosis rate, and determined about a third of diagnoses within genes that were previously thought to be entirely unrelated to mitochondrial disease.

For Melbourne teenager Tyler Caulfield, the struggle to be diagnosed with the little-known disease took almost five years, leaving him without pediatric care during a critical period.

“In grade two, his teacher noticed there was something not quite right, and he was falling behind and slow to start tasks, so he ended up doing an auditory processing assessment,” Tyler’s dad, Leigh Caulfield, said.

In 2020, Tyler was diagnosed with mitochondrial deletion syndrome which significantly hampered his hearing, vision and energy levels. Now at age 15, Tyler is legally blind.

Tyler Caulfield, 15, has mitochondrial deletion syndrome, which has left him legally blind.

“It’s gotten worse and worse. So he’s only got about 10 degrees of vision left now,” Mr Caulfield said.

“He’s put two and two together; he knows he’s not going to be getting his driver’s licence. He’s always wanted this bright green ute, so the realisation of all that has been pretty difficult.

“He withdraws from things, from doing stuff, because he doesn’t want to hurt himself. So he just wants to be a bit insular and stay inside and doesn’t go anywhere. It’s always a challenge to get him out and about.”

Roughly one in 5000 Australian children are born with mitochondrial disease.

Genomic screening relies on highly detailed analysis of the genome in certain cells to learn their unique differences in certain genes and proteins.

It was found to be less effective in diagnosing mitochondrial disease in adults, with a 31 per cent success rate given mitochondrial DNA genetic variations in adult blood can decline with age, and even become undetectable.

While current treatments focus on minimising symptoms, pilot programs are investigating the efficacy of mitochondrial donations as a potential means of slowing disease progression.

“Even if there isn’t a treatment, you could still have improved management and allow these patients to avoid invasive and expensive testing,” said MCRI’s David Thorburn.

Murdoch Children’s Research Institute geneticist David Thorburn.

“This paper is the consequence of the genomics revolution that’s happened over the last 15 years or so.

“This paper was not just about diagnosing lots of patients, but about making sure even when the clinician might be asking the wrong question, you can still get the right answer. This test potentially tests for all inherited diseases.”

The peer-reviewed observational study will also be integral to the genetic screening of parents who wish to determine the likelihood of a future child developing mitochondrial disease.

“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,” Professor Thorburn 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 MCRI recruited 140 children and adults for the study to determine genetic causes of dozens of strains of the disease.

MitoHOPE director Sean Murray.

When speaking on the struggle of families grappling with the condition, MitoHOPE charity chief executive Sean Murray said “uphill is an understatement”.

“What we’re finding is that the more we find out about it, the broader the implications of mitochondria are on our health generally,” he said, “and therefore the scope of this disease is really broadening.

“It really is encouraging to see that this group of disorders are starting to get the attention that we’ve always felt that they deserved, because for so long they’ve been under-addressed, under-resourced, and under-invested in.”