Scientists at The Kids Research Institute Australia, together with the Undiagnosed Diseases Program and Perth Children’s Hospital (PCH), combined medical expertise with laboratory investigations and cutting-edge computational biology to uncover a unique combination of cellular characteristics which pinpointed the cause of an undiagnosed disease that has puzzled doctors since 10-year-old Northam girl Charlotte Patterson was born.
The researchers then scoured literature and data from around the world to find other patients with similar traits to match the findings to the condition, which they now believe affects less than 10 people globally.
The findings were delivered to Chalotte’s family by doctors from the Undiagnosed Disease Program (UDP) at PCH.
The quest to find the cause of Charlotte’s) condition started in 2019 and was boosted in 2020 by a donation of more than $1.1 million raised at that year’s Channel SevenTelethon Ball.
The Kids’ Precision Health Program Head and computational biologist, Dr Timo Lassmann, said discovering the characteristics of the variant gene which caused Charlotte’s disease was like finding a needle in a haystack.
“Charlotte’s case was extremely complicated and challenging because of the unique characteristics of the variant,” Dr Lassmann said. “Now, as a result of this work, we will be able to apply the process we used to other cases to diagnose unknown diseases more quickly.”
In her short life Charlotte has been diagnosed with cerebral palsy, seizure disorder, a heart defect, intellectual disability and many physical abnormalities that until now, have been unexplained. She has had 64 surgeries, takes 16 different medications daily and requires a feeding tube.
Her mother, Laura West, said it had been extremely difficult for the family to not know what caused Charlotte’s condition.
“We had no roadmap, no idea what the future might look like or what her lifespan might be,” Mrs West said. “We have just had this endless and ever-growing list of things that are wrong with Charlotte and no idea what caused any of them.”
The Kids’ Translational Genetics Team Head, Dr Vanessa Fear, said the discovery of what caused Charlotte’s condition was astounding. After a complicated process of assessing the genetic variant in the laboratory, The Kids’ researchers discovered the variant was actually changing the basic machinery in cells responsible for the gene and protein expression, and altering the way the neural cells were developing.
Dr Fear said researchers had created a model of Charlotte’s disease in the laboratory so they could not only determine what was causing her symptoms, but also investigate how they could modify cell pathways to improve outcomes for Charlotte.
“I am just really proud to have been a part of this process where so many people have worked every little step of the way, from collecting blood samples to analysing the cells, to finally providing this extremely valuable data we could feed back to Charlotte’s clinician and her family,” Dr Fear said.
UDP lead Dr Gareth Baynam said families with a child with an undiagnosed disease were forced to live in ‘limbo land’ where their world was filled with uncertainty.
“You don’t know what the right treatment is, and you don’t know if you’re receiving the wrong treatment,” Dr Baynam said. “What I hope is that through getting this diagnosis it really does help Charlotte have better health, to have a better medical home and to have more certainty about what the future brings.
“We can now unequivocally say that Charlotte is going to have a long life. She is not going to go backwards, there is a path forward.”
Mrs West said receiving a diagnosis for Charlotte was life-changing for her family. “It gives us hope for the future,” she said. “I think the best bit was learning that this specific gene variant has just occurred out of the blue. It was something that happened and it not hereditary and can’t be passed on.” This was particularly important for Charlotte’s three siblings.
Dr Lassmann said the case underscored the vital role of collaboration between clinical and research teams and highlighted the value of translational genetics teams taking on the most difficult cases.
The Kids Executive Director, Professor Jonathan Carapetis, said the discovery was groundbreaking and set up a pipeline for similar breakthroughs in rare and undiagnosed diseases.
“The work The Kids’ computational biology team is undertaking is world-leading,” Professor Carapetis said. “They are using cutting-edge technologies and computational science to unlock some of the biggest medical mysteries and help other children with undiagnosed diseases.”