Mainstreaming genomic testing for mitochondrial disease in Australia

Genomic sequencing has transformed the diagnostic approach for mitochondrial disease, yet integration into standard clinical practice is limited by access and funding. We conducted a post-implementation evaluation of genome sequencing (GS) for mitochondrial disease in Australia, which became publicly funded through the Medicare Benefits Scheme (MBS) in November 2023, to allow for broader access to testing. Test request data, including demographics, phenotypic information, and the diagnostic outcomes, were collected from November 2023 to May 2025 from the Victorian Clinical Genetics Services, the current laboratory provider of the MBS-funded service. Test uptake was 26% of predicted, with lower test rates in regional and remote areas. Over the first 19 months, 300 individuals suspected of mitochondrial disease underwent GS with a median turnaround time of 84 days (8 days-218 days). The diagnostic yield was 20%, with 56% of diagnoses in known mitochondrial disease genes. Of these, 70% (24 of 34) were in mitochondrial DNA. Seventeen diagnoses were in individuals who had prior non-diagnostic testing (exome sequencing or gene panel). We demonstrate that publicly-funded GS can deliver meaningful diagnostic outcomes for mitochondrial disease on a national scale. To maximise its impact, attention must now shift towards ensuring equitable access, particularly for regional and remote areas, and embedding sustainable mainstreaming models that support both genetic and non-genetic clinicians.