Faster diagnosis hope for mitochondrial disease

A new approach to genetic analysis may lead to a faster way to diagnose mitochondrial disease.

A study led by Australian researchers linked mutations in a gene called MRPS34 with one of the most common childhood mitochondrial diseases, Leigh syndrome. It identified the gene using a strategy called quantitative proteomics – which can identify and compare all the proteins in a sample.

'This approach will therefore help to end the diagnostic odyssey for families with children suspected of mitochondrial and other inherited diseases,' said Professor David Thorburn, the study’s lead author at the Murdoch Children's Research Institute (MCRI) in Melbourne.

Until recently, diagnoses for mitochondrial diseases were extremely slow, with only a quarter of patients receiving one, according to the Australian Mitochondrial Disease Foundation (AMDF). It says that the advent of whole exome sequencing technology means that now two-thirds of patients get a diagnosis. 'However other approaches are needed to identify the difficult cases that continue to elude,' it said.

The researchers identified the new gene implicated in Leigh syndrome by analysing all the proteins produced by skin cells cultured from six patients compared with those from healthy volunteers.

'A key approach was using quantitative proteomics. This process involves sampling all the proteins in a cell at once to identify any problems with the cellular machinery,' said Ms Nicole Lake, a PhD student at MCRI, and study author. 'Using this technique, you get a snapshot of what’s happening in cells.'

By examining the proteins, the team found that part of the cellular machinery that mitochondria use to manufacture proteins themselves – called the 'mitoribosome' had fallen apart in patients with Leigh syndrome.

They also showed that MRPS34 was pivotal in the functioning of the mitoribosome, confirming that the gene mutations were a cause of the mitochondrial disease.

The researchers hope the approach might lead to quicker diagnoses and therefore earlier and more targeted treatments for patients with mitochondrial diseases.

The AMDF called the study an 'exciting development'. 'I'm particularly thrilled to see an outcome like this,' said Sean Murray, the foundation's CEO.

The research was published in the American Journal of Human Genetics.