World-first discovery transforms Freddie's life

World-first discovery transforms Freddie's life

Freddie smiling in bed in hospital as a baby

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. 

Freddie in hospital as a baby

Rather than healing, the wound broke down following surgery, leaving Freddie seriously unwell. This was the beginning 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.

Genetic testing undertaken by Professor Edwin Kirk, clinical geneticist at SCH and genetic pathologist at NSW Health Pathology’s Randwick Genomics Laboratory, revealed a genetic 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 researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne. 

Freddie smiles in hospital bed as a baby

At WEHI, Professor Seth Masters and Dr Sophia Davidson, experts in genetic inflammatory diseases, and Prof David Komander, a world expert on OTULIN deficiency, modelled Freddie’s genetics and discovered Freddie had OTULIN deficiency caused by a single dominant negative change in his gene. 

OTULIN deficiency is extremely rare, with only five cases previously recorded worldwide, and Freddie the first to be discovered with this specific inheritance. 

“With Freddie in a critical condition, expert collaboration between scientific and medical experts was vital to discover exactly what was wrong and why in real time,” A/Prof Gray said.

“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.”

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

“Paediatric surgeon Carolyn Russell performed twice weekly vacuum dressings, a massive job which encouraged the wound to close, while general paediatrician Anna van Beek went the extra mile to help Freddie grow and prepare him for his definitive surgery,” A/Prof. Gray said.

“In what was a whole of hospital effort, Freddie grew, and the tummy wound closed slowly until it was small enough to perform another surgery on.”     

It was a long and uncertain road to recovery, but thankfully, Freddie’s condition began to stabilise.

“He was such a fighter, every day, every challenge, he just got through,” Katrine said.

“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 care has been extraordinary, thanks to the staff at SCH. The doctors and nurses in the CICU saved his life several times, for which we will be eternally grateful,” Katrine said.

“Dr Russell has taken such good care of us, working tirelessly to save our boy and coming up with solutions to near impossible problems, and Dr Gray has been so committed to Freddie’s care. Without his expertise and incredible knowledge, I am not sure our boy would be here with us. He and his team continue to be a driving force behind Freddie’s ongoing treatment.”

The ultimate example of personalised medicine and multidisciplinary care, Freddie’s case was recently published in the prestigious Journal of Experimental Medicine. The evidence that came from it has already helped another child discovered with the same condition caused by the same mutation in Saudi Arabia.