Faster genetic diagnosis for critically ill babies and children in Australia

Rapid genomic testing will soon be available to critically unwell Australian babies and children with suspected genetic conditions, as part of four new national genomic research studies launched by Australian Genomics.

From next month, the Acute Care Genomics study will enrol infants and children with suspected genetic conditions from intensive care units across much of the country. The study aims to provide genomic test results in as little as five days to quickly pinpoint the cause of the child's condition and inform their clinical care. Rapid genomic testing is currently only available at a handful of centres worldwide, and the study will be the first to pioneer a national approach to rapid rare disease diagnosis.

The Acute Care Genomics study is co-led by A/Prof Zornitza Stark, A/Prof Marcel Dinger, and Dr. Sebastian Lunke. A/Prof Zornitza Stark is a clinical geneticist at Victorian Clinical Genetics Services (a wholly owned not-for-profit subsidiary of the Murdoch Children's Research Institute), and The Royal Children's Hospital, and has conducted pilot studies demonstrating the clinical and economic benefit of applying genomic testing early in rare disease diagnosis.

"Time is absolutely precious when providing care to sick babies and children in intensive care units," A/Prof Stark said. "At the moment, turnaround times for genomic results can be up to six months, which is far too slow to help families and clinicians caring for children in intensive care. We have already seen the benefits of early rare disease diagnosis locally, and will be extending testing across much of Australia, while providing clinical results in as little as five days."

DNA samples collected from 250 infants and children being cared for at 18 neonatal and paediatric intensive care units in Australia will be sent to Genome.One and to Victorian Clinical Genetics Services for rapid testing. At each stage of the process from the DNA preparation and genomic sequencing, to bioinformatic analysis, diagnosis and return of results, teams at both centres will streamline processes and sharpen technological capabilities, to enable return of results at a speed that is unprecedented in Australia.

"We're continuously refining our approaches, and innovating to make the process more efficient at every stage to be able to provide genomic information to where it can be best used within a meaningful timeframe," said A/Prof Marcel Dinger, CEO of Genome.One, a wholly-owned subsidiary of the Garvan Institute of Medical Research, and Head of Garvan's Kinghorn Centre for Clinical Genomics

"This is about genomic technology fulfilling its promise," said Dr. Lunke of the Translational Genomics Unit at Victorian Clinical Genetics Services. "We're pushing the limits of what we thought possible and changing practice in real time. We want to be able to say to clinicians in intensive care units that we can help them piece together what's going on, and we can do it quickly."

The Acute Care Genomics study has been established with the support of The Royal Children's Hospital Foundation, the Sydney Children's Hospital Network, Garvan Institute of Medical Research and Australian Genomics.

A/Professor Meredith Wilson, Head of the Department of Clinical Genetics at The Children's Hospital at Westmead (Sydney Children's Hospital's Network) said, "As a clinician, I see this flagship research is an opportunity to demonstrate how providing information rapidly can help both to support families at a crucial time and to guide doctors in acute care. A diagnosis at an early age can also provide vital information to families for their future plans." 

"The RCH Foundation is proud to support The Royal Children's Hospital's involvement in Australian Genomics and this pioneering project, which will greatly improve the lives of many sick children and their families across the country," said Sue Hunt, Chief Executive Officer, RCH Foundation. 

In addition to the Acute Care Genomics study, Australian Genomics announced three other national studies, similarly trialling how genomics can provide diagnostic certainty and change practice.

These studies will investigate whether genomics can:

• Improve the diagnosis of rare chronic lung disorders in children and standardising clinical practice for these diseases in Australia. The 'chILDRANZ Flagship' study, led by Prof. Adam Jaffe (University of New South Wales and Sydney Children's Hospital), builds upon an Australian and New Zealand network of doctors and researchers collaborating globally to improve healthcare for children affected by rare chronic lung disorders. In harnessing genomic technologies, this national Flagship study aims to improve the diagnosis, clinical management and referral practices for these disorders in Australia. The Flagship collaborates with the Lung Foundation Australia.
   
• Better diagnose cardiovascular disorders, at less cost. The 'Cardiovascular Genetic Disorders Flagship' is led by Prof Chris Semsarian (The University of Sydney & Centenary Institute) and A/Prof Julie McGaughran (Genetic Health Queensland). The study is gathering information on the clinical and economic outcomes of genomic testing among children and adults with a cardiovascular disorder and also exploring the impact of genomic testing within families. The researchers aim to determine how genomic approaches can inform a unified, standardised and sustainable approach to cardiac genetic testing in Australia.
   
• Provide a clinical diagnosis for patients with end-stage kidney disease of unknown cause. The 'HIDDEN Renal Genetics Flagship', is led by Dr. Andrew Mallett (Royal Brisbane and Women's Hospital and The University of Queensland) and the KidGen Collaborative.  'Unknown cause', in end-stage kidney disease (ESKD), describes those without a definitive diagnosis, despite an overwhelming excess burden of morbidity and mortality that these patients experience. The 'HIDDEN' study builds upon the KidGen Collaborative and partnership with Kidney Health Australia, to trial whether genomic testing approaches can improve the diagnosis and clinical management of patients with ESKD of unknown cause.

Professor Kathryn North is the Director of Murdoch Children's Research Institute and leads Australian Genomics. Professor North said of these latest studies, "We're delighted to commence these new clinical Flagship projects, which join another 11 already underway. It's fantastic to see such a range of great research programs in Rare Diseases and Cancers, connecting 400 researchers and collaborators, and demonstrating the multiple clinical applications of genomics across the country."

The Acute Care Genomics study will formally commence recruitment from 12 hospitals next month, with the lung disorders, cardiovascular and kidney studies similarly gearing up to enrol participants. These latest studies will run for two years.