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Improving the Diagnostic Process for Patients with Mitochondrial Disease

Northern Sydney Local Health District
Project Added:
19 October 2016
Last updated:
21 April 2021

Improving the Diagnostic Process for Patients with Mitochondrial Disease


This project developed next-generation sequencing ( NGS ) protocols and a bioinformatics platform for diagnosing mitochondrial disease, as well as a diagnostic pipeline that improved the speed and accuracy of diagnosis.


To increase the number of genetically-diagnosed patients with mitochondrial disease in Northern Sydney Local Health District ( NSLHD ) by 50% within 12 months.


  • Reduces delays in diagnosing patients with mitochondrial disease.
  • Allows patients to be diagnosed with a simple blood test.
  • Reduces the need for multiple visits to doctors and unnecessary investigations, including muscle and liver biopsies.
  • Provides patients who have mitochondrial disease with appropriate treatment and care.
  • Reduces the costs associated with unnecessary investigations, clinical reviews and treatments.
  • Accurately sequences the DNA of mitochondrial disease and identifies the genetic mutation causing the disease.
  • Improves the health and safety of patients with mitochondrial disease and their families.


Genetic testing for many inherited conditions is not freely available or accessible in Australia. Mitochondrial disease is the most common form of inherited metabolic disease. Individuals with this disease may present with a range of symptoms that often masquerade as other diseases. This makes the diagnosis of mitochondrial disease very difficult.

Patients with mitochondrial disease often see multiple doctors and bounce from one health service to the next in their attempt to be accurately diagnosed. They may undergo multiple tests and sometimes invasive investigations, such as muscle or liver biopsies. Specialised clinics with the necessary expertise are rare and often do not have the resources to meet clinical demand. As a result, patients with mitochondrial disease often fail to receive appropriate care and remain undiagnosed or misdiagnosed. They may also be administered medications that are harmful to their disease.

Mitochondrial disease is best managed with early treatment. Patients should receive genetic counselling to support family planning, with access to specialised IVF techniques that prevent the disease from being passed to their children. If eligible, they should also be provided with an opportunity to access disease-specific treatments or clinical trials.

It was determined that developing a simple, accessible and affordable genetic test will improve the treatment and care of patients with mitochondrial disease and their families.


  • 250 patients in NSLHD with suspected mitochondrial disease were given blood tests for genetic mutations, using advanced methods to perform DNA sequencing.
  • A bioinformatics platform to read sequencing results was developed, which analysed and identified genetic mutations in both the mitochondrial and nuclear genomes.
  • An in-house diagnostic pipeline is currently being built, which uses multiple software programs containing NGS to accurately and efficiently diagnose patients with mitochondrial disease.

Project status

Implementation - the initiative is ready for implementation or is currently being implemented, piloted or tested.

Key dates

November 2015 – November 2016

Implementation site

Department of Neurogenetics, Royal North Shore Hospital, NSLHD


  • Royal North Shore Hospital
  • NSW Office for Health and Medical Research
  • The Kinghorn Centre for Clinical Genomics, Garvan Institute for Medical Research
  • Clinical Excellence Commission, Clinical Leadership Program
  • The Kolling Institute
  • Children’s Hospital Westmead
  • Charles Perkins Centre, University of Sydney


  • Genetic mutations were identified in over 50% of the patient cohort. Around half these mutations resided in the mitochondrial DNA and the other half were located in nuclear genes.
  • All genetic mutations identified in the project will be confirmed using direct (Sanger) sequencing. The primary outcome will measure the number of patients with mitochondrial disease, identified by causative genetic mutations.
  • An analysis is currently underway to determine the cost-effectiveness, diagnostic accuracy and time to diagnosis of mitochondrial disease, using the NSG protocols developed in this project.

Lessons learnt

The volume of data generated by the new NGS protocols is considerable and as such, the analysis of results is not straight forward. Further development of the diagnostic platform is needed, to optimise the sensitivity of NGS protocols so that all causative mutations are accurately identified.


  • Calvo SE, Compton AG, Hershman SG et al. Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing. Science Translational Medicine 2012; 4(118): 118ra10.
  • Daily Telegraph. [Internet]. $740,000 will help researcher Carolyn Sue and her team to diagnose mitochondrial disease; 2015 Mar 12 [cited 2016 Oct 19].
  • Liang C, Ahmad K, Sue CM. The broadening spectrum of mitochondrial disease: shifts in the diagnostic paradigm. Biochimica et Biophysica Acta 2014; 1840(4): 1360-1367.
  • Lieber DS, Calvo SE, Shanahan K et al. Targeted exome sequencing of suspected mitochondrial disorders. Neurology 2013; 80(19): 1762-1770
  • Sue CM. Mitochondrial disease: recognising more than just the tip of the iceberg. Medical Journal of Australia 2010; 193(4): 195-196.


Professor Carolyn Sue
Head and Director of Neurogenetics
Northern Sydney Local Health District
Phone: 02 9463 1828

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