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The research collaboration that helped save a little boy’s life 

24 April 2024
Key Researchers
Division Head
Freddie smiling

When Freddie was diagnosed with a rare genetic condition just a few days after he was born, it marked the beginning of a series of health complications that left the newborn critically ill.

But a research collaboration between WEHI and Sydney Children’s Hospital solved a mystery that has now transformed his life.

Beating the odds

Freddie might only be three years old, but he has already made history as the first person ever recorded with his extremely rare genetic condition.

Following an incredibly challenging beginning to life for Freddie and his family, his parents Katrine and Paddy marvel at the remarkable transformation in their little boy.

Once critically ill in hospital, he has grown into a playful toddler radiating with energy and infectious smiles.

Born at just 31 weeks gestation due to a pregnancy complication called sudden onset preeclampsia, Freddie initially appeared to be quite healthy for a premature baby.

However, just a few days into his life, what was believed to be an abscess was discovered near Freddie’s belly button, requiring surgical intervention.

Rather than healing, the wound broke down following surgery, leaving him seriously unwell. This marked the start of a series of serious health complications over the coming months.

Freddie was admitted to the Children’s Intensive Care Unit (CICU) at Sydney Children’s Hospital, Randwick (SCH) where the wound was initially treated as an infection. But it soon became clear that the cause was inflammation, prompting further investigation.

Freddie as a baby wearing a nasal gastric tube
Freddie became the first patient to be diagnosed with this specific variant of ORAS just a few days after he was born. Credit: SCHN

Rare discovery

Genetic testing revealed a change in the gene involved in the regulation of inflammation. 

Suspecting potential OTULIN Related Autoinflammatory Syndrome (ORAS), paediatric immunologist and allergist Associate Professor Paul Gray and the immunology team at SCH contacted WEHI researchers Professor Seth Masters, Dr Sophia Davidson  and Professor David Komander. 

ORAS is a rare disorder leading to chronic inflammation, fever, and joint pain, caused by mutations in the OTULIN gene.

Prof Komander, head of WEHI’s Ubiquitin Signalling division, is a world expert on OTULIN, while Dr Davidson and Prof Masters (now at the Hudson Institute), are experts in genetic inflammatory diseases. 

The team modelled Freddie’s genetics and discovered he had ORAS, caused by a single dominant negative change in his gene.  

Professor David Koamnder
Professor David Komander is a world expert on OTULIN after discovering it in 2013. Credit: WEHI

Transformative collaboration

Prof Komander, who discovered and named OTULIN in 2013, says it is humbling to know their previous work has helped to make a real clinical impact. 

“The discovery led to the identification of a severe autoinflammatory disease, which has been named OTULIN-related autoinflammatory syndrome – or ORAS,” he says. 

“Freddie has a new variant of ORAS where just one of the two copies of the gene is mutated. He’s the first patient to be discovered with this specific inheritance. 

“Our team was able to analyse his blood and genes to find the culprit for his unhealed wound, which subsequently led to the design of a new treatment plan. 

“ORAS is also now firmly anchored in the field of rare inflammatory diseases, and importantly, we understand how patients should be treated to alleviate the symptoms and how they need to be monitored to prevent future complications.” 

Dr Sophia Davidson led the research team that analysed Freddie’s blood, ultimately underpinning why the child had been struggling with a stubborn wound for months.

“Our team was able to analyse Freddie’s blood and genes to find the culprit for his unhealed wound, which subsequently led to the design of a new treatment plan.

“The impact was revolutionary – the wound healed, and this toddler is now happily enjoying life to its fullest.”

In the weeks after this discovery, a truly multidisciplinary team including immunology, surgery, and general paediatrics at SCH, worked together to provide tailored care for Freddie’s condition.  

SCH’s Associate Professor Paul Gray says the expert collaboration between scientific and medical experts was vital. 

“At times along this journey, the chances of survival were low, but he had committed medics, modern science and his incredible parents, Paddy and Katrine,” Assoc Prof Gray says. 

Dr Sophia Davidson
Dr Sophia Davidson led the research team that analysed Freddie’s blood. Credit: WEHI

Thriving toddler

While the road to recovery was long and uncertain, thankfully, Freddie’s condition began to stabilise. 

“He was such a fighter, every day, every challenge, he just got through,” Katrine, Freddie’s mum, says. 

“My husband and I were just in awe of him. He’s just got so much courage and bravery.” 

Now more than 18 months on from his surgery, with ongoing support and targeted treatment, Freddie is thriving, and his future is looking bright.  

Freddie’s case was recently published in the prestigious Journal of Experimental Medicine, with Dr Davidson the lead author on the paper.

The evidence already helping another child discovered with the same condition caused by the same mutation in Saudi Arabia.  

Header image: The research collaboration between WEHI and SCH helped Freddie go from being a critically ill newborn to a thriving toddler. Credit: SCHN

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