Breaking the code

Article from 2019/2020 Impact of Giving Annual Report

Time is precious when diagnosing sick babies and children in intensive care. If the cause of their condition cannot be explained, clinicians must work through a process of elimination to get the right diagnosis and treatment. However, this can involve extensive and invasive tests, negatively impacting the child and their family during the critical moments of their hospital stay.

One in 17 Australians have a rare genetic disease, most of them children. The most accurate way to find the cause of their illness is to examine their genes. Thanks to your generous support, the Acute Care Genomics study is continuing to provide rapid genomic testing to unwell Australian babies and children with genetic conditions, finding answers for families faster than ever before.

Genomics is the study of the genome, which is the unique set of DNA or genetic instructions of living organisms. Clinical geneticists work like codebreakers, examining a person’s unique sequence to find genetic variations or mutations in the code which may explain a medical condition.

Professor Zornitza Stark is the clinical lead for the ground-breaking Acute Care Genomics study and a clinical geneticist at the RCH and the Victorian Clinical Genetics Services (VCGS).

“When human DNA was first sequenced for the Human Genome Project in 2003, the endeavour took 10 years and cost over $10 billion. Now with the latest medical advancements, ultra-rapid genomic testing takes just days, and can be performed as part of routine medical care, resulting in much better outcomes for families,” said Zornitza.

When a patient being cared for in the RCH Neonatal Intensive Care Unit (NICU) or Paediatric Intensive Care Unit (PICU) has a suspected underlying genetic disorder, the treating team refer them to the clinical genetics team for assessment. If they think a genetic condition is likely, blood samples are collected from the patient and their parents for processing. All the DNA is then rapidly sequenced and analysed, with families then receiving support from a multidisciplinary team of geneticists, medical specialists, nurses, social workers and genetic counsellors who communicate the complex genetic information so they are informed and able to make the best decisions for their child.

“Since its introduction in 2018, the program has been able to provide results to families in an average time of three days, a process which usually took six months. This is also the fastest average reported time by any rapid diagnosis program in the world,” said Zornitza.

The ultra-rapid genomic testing has led to 51 per cent of patients receiving a diagnosis, relieving the emotional stress for families who were previously faced with the unknown. It has also led to changes in the clinical care a patient receives in 75 per cent of those diagnosed.

“Ultra-rapid genomic results in ICU mean an end to invasive tests for a child and reduce uncertainty for the family and treating teams. It allows parents to better understand why their child is sick, how to manage their condition and how to plan for the future. For a small number of children, a timely diagnosis enables precision treatments,” said Zornitza.

For parents Viola and Nolan, the results of genetic testing meant they had a diagnosis for their critically ill baby boy Ayden. Despite the results being devastating as his condition was life-limiting, the family were able to spend a precious last few months together and make decisions when planning to have another baby to ensure it would not be born with the same condition.

Despite the challenges of hospital care during COVID-19, the Acute Care Genomics study has been able to continue, having already transitioned to a virtual workflow before 2020. Patient cases are reviewed by a virtual panel, consent is provided electronically by families, test ordering is processed online, and genetic counsellors are able to talk to families over the phone or video call to step them through the testing process and results.

The Acute Care Genomics study is made possible thanks to significant collaboration between the RCH, MCRI and VCGS, which is strengthening the position of the RCH campus as national and international leaders in paediatric clinical genomics. With the success of the study, the campus partners have now set up a national network, collaborating with other children’s hospitals across Australia so they can send DNA samples to the RCH for testing. The Acute Care Genomics study has provided expertise and advice to other centres in the United Kingdom, New Zealand, Canada and the United States of America seeking to establish similar programs.

The continuation of funding from the RCH Foundation is now expanding the capacity of the Acute Care Genomics study with the aim to further improve turnaround times and diagnostic yield of genomic tests by transitioning from rapid whole exome to whole genome sequencing.

“Whole exome sequencing analyses one per cent of the genetic material, whereas whole genome sequencing looks at all the genetic information. Differences in sample processing mean we can reduce the laboratory turnaround time further while providing a more comprehensive picture of the genes of patients and families,” said Zornitza.

With research and clinical practice working hand in hand, Acute Care Genomics is paving the way for future advancements in children’s healthcare with precision medicine providing accurate treatment for the sickest patients.