Cutting the diagnosis journey for children born with rare genetic diseases
Families can wait years for a diagnosis of a rare genetic disorder, but a new test can provide answers in days for a better understanding of the condition and potentially earlier treatment
Published 23 May 2025
In its standard definition, the word ‘rare’ describes something that doesn’t happen very often.
So families who receive a diagnosis of a ‘rare genetic disease’ understandably feel isolated and that their situation is indeed uncommon.
But in reality, when all diagnoses of ‘rare genetic diseases’ in Australia are combined, they affect about 2 million people or around 8 per cent of our population.
Despite affecting so many individuals and families, the journey to a diagnosis can still be long and complicated.
Thanks to the genomics revolution, around 50 per cent of families receive a diagnosis within months, but many others endure a ‘diagnostic odyssey’ of additional tests that can take years or never be achieved.
To improve this situation, our team have now developed a diagnostic test to give families answers sooner.
What is a rare genetic disease?
Our research focuses on rare genetic diseases caused by a single gene alteration or mutation, known as monogenic disorders.
These diseases include cystic fibrosis and mitochondrial disease – a group of severe disorders that rob the body’s cells of energy, causing single or multiple organ dysfunction and potentially death
There are approximately 7,000 different rare diseases, and sadly, no treatment for many of the conditions. They are usually devastating in many ways, often leading to death within the first few years of life.
Diagnosis is not only important for understanding the disease state of the child, but it may also enable access to treatment or clinical trials and provide families access to reproductive planning approaches to have a healthy child.
Current diagnostic environment
The ‘diagnostic odyssey’ is the phrase often used to describe the journey of patients with an uninformative result following genomics analysis, going from follow-up test to test, hospital to hospital and even specialist to specialist in order to diagnose their disease.
Many patients can now access genome sequencing, which is very effective in diagnosing ‘known’ or ‘previously identified’ mutations.
Unfortunately, this is only successful in about half the cases, with others typically having only ‘variants of uncertain significance’, which are mutations that have not previously been shown to cause disease, and some patients can receive this result for multiple genes.
In these cases, one or multiple functional tests are required to understand what effect the genetic mutation has on the body, which typically takes time.
Moreover, some of these tests are invasive, painful procedures involving muscle biopsies that can be traumatic and require a general anesthetic for babies and children.
A new type of diagnosis
Our new diagnostic test, published in the journal Genome Medicine, sits parallel to genomic sequencing and helps interpret the sequencing data in a very rapid way.
The test is not specific to a single rare disease, or even a single type of mutation for a specific disease and can potentially replace thousands of different functional tests.
We are using proteomics, the study of proteins and their composition in our cells and body fluids, in a high-throughput way, as a tool for rapidly interpreting the effect of mutations identified in genome sequencing data for about half of the known rare disease genes.
We have developed a blood-based version of the test that is effective in diagnosing rare diseases, even in critically ill babies in neonatal intensive care.
Historically, comparable tests have a turnaround time of weeks and sometimes months, but our blood-based proteomics test can return results in as little as three days.
A recent health economics analysis by the Melbourne School of Population and Global Health also showed that our test could be offered at a similar cost to the one offered clinically for mitochondrial diseases.
The new test was found to be much more cost-effective as it can analyse thousands of different gene mutations that have already been associated with diseases, whereas most current functional tests are targeted and only test for a small number of genetic defects.
One family’s journey
For parents Corina and Destiny, this new diagnostic protocol has been critical for their current and future pregnancy management.
Corina and Destiny lost their first child, Ahi o Te Aroha, at six months old. Although genetic testing identified a variant in a gene associated with mitochondrial disease, this variant was of uncertain significance as it had not been previously reported.
At the time the genetic result was received, Corina was in the early stages of her next pregnancy, and they were concerned their child could suffer from the same condition.
At six weeks gestation, their clinician contacted us to help confirm the cause of the disease for Ahi o Te Aroha so that the risk for the current pregnancy could be determined.
We were able to perform our diagnostic test using stored samples from the deceased daughter Ahi o Te Aroha, confirming the diagnosis and giving a clear understanding of the family’s genetic situation.
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The family was then able to undergo prenatal genetic testing – genetic testing of the foetus in early pregnancy – which showed the unborn baby had not inherited the same genetic disease.
The pregnancy continued to term, resulting in the birth of a healthy son. He is now three years of age, and they are expecting another baby this year.
Corina and Destiny expressed their deepest gratitude. They hope that other families can benefit from this testing to prevent further loss and help the grieving process by promoting understanding and acceptance.
Next steps
Following a $AU3 million Australian Government Medical Research Future Fund grant, we are now recruiting 300 patients with a range of different genetic disorders to investigate the utility of the test for a range of conditions.
Our ultimate goal is for the test to be offered nationally through the Victorian Clinical Genetics Services, supporting as many children and families as possible.