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SickKids research team identifies a new disease and solves a medical mystery
7 minute read

SickKids research team identifies a new disease and solves a medical mystery


In a paper published online in Nature Communications, a team of SickKids clinician-scientists led by Drs. Aleixo Muise and Walter Kahr report the discovery of a new hereditary condition: ARPC1B deficiency.

Two men stand side by side in a lab, wearing lab coats.
Drs. Muise and Kahr.

TORONTO – In a paper published online in Nature Communications, a team of SickKids clinician-scientists led by Drs. Aleixo Muise and Walter Kahr report the discovery of a new hereditary condition: ARPC1B deficiency. In addition to providing key clues concerning how our bodies, organs and cells work, this study provides a surprising answer to a medical mystery that began seven years ago, when Muise met a toddler with some very serious symptoms.  

Daniel Nevins-Selvadurai was three years old when he was admitted to SickKids with constant bleeding when he went to the washroom. When staff gastroenterologist Muise saw Daniel in clinic, he quickly recognized the signs of inflammatory bowel disease (IBD). When IBD appears in very young patients there is usually a hereditary cause. But when Daniel was tested, he came up negative for the gene mutations known to cause IBD.

Young boy stands in hallway with IV pump.
SickKids patient Daniel Nevins-Selvadurai, who was diagnosed with ARPC1B deficiency.

Daniel’s situation became more severe and puzzling as he got older. Unlike most IBD patients, he developed unusual rashes and inflammation in his legs, ankles, feet and blood vessels (vasculitis). He also had blood abnormalities like high white cell and low platelet counts. These symptoms suggested problems in Daniel’s immune system. “It was Daniel’s father who noticed that while other kids got coughs or colds, for Daniel that infection would manifest as a painful rash or vasculitis,” says Daniel’s mom, Christina Arulrajah.

Daniel was referred to a number of SickKids clinical teams in haematology, oncology, rheumatology, immunology, gastroenterology, dermatology and other specialties. They all did their best to address his painful symptoms, but none were able to tell Daniel and his family what was causing them.

In late 2014, Muise with other SickKids collaborators launched a major project to explore the genetic basis of IBD and similar diseases using advanced DNA sequencing techniques. “As we sequence the genomes of these rare patients, it is always exciting because we are uncovering novel mutations and identifying diseases that have never been studied before,” says Muise, principal investigator of this study and Staff Gastroenterologist at SickKids.

Daniel’s unique symptoms made him an ideal candidate for this study, and after an extensive search Muise and his team found a mutation in his DNA that no one had seen before. The result came as quite a surprise to the research team because the mutation was in ARPC1B. This gene produces a core protein of the Arp2/3 complex, which our cells need in order to change shape, move, divide and perform other vital functions.

“At that time, most cell biologists would have told you that we cannot live without ARPC1B protein,” recalled Kahr, the study’s lead author who is a staff haematologist and senior scientist at SickKids. “But when we examined Daniel’s platelets we found that this protein was completely missing.”

Team of twelve staff look over a railing from a balcony. Photo taken from below.
This work is a result of a uniquely SickKids clinical and research collaborative team.

Muise and the team subsequently discovered two other patients that were related to each other but not to Daniel, who had mutations that left them with very little ARPC1B protein. They had some of the same symptoms as Daniel, and like him they also had unusually small and oddly-shaped platelets. This abnormality had previously only been seen in patients with Wiskott-Aldrich syndrome, who often also have severe immune problems. When platelets from Wiskott-Aldrich syndrome patients are allowed to spread on a surface they form little discs, just like normal platelets. In contrast, Kahr’s group observed that when platelets from the ARPC1B-deficient patients spread they sprouted bizarre spider-like tendrils.

“As a cell biologist and a haematologist who treats children with platelet disorders, it was surprising to come up with these completely new insights into how platelets work,” says Kahr. “This research demonstrates how observations made in the clinic and the laboratory can complement each other to help us understand patient problems, advance basic knowledge and translate research into new opportunities for improving care.”  

The results certainly made a big impression on the person who matters most. “Daniel was over the moon to get a diagnosis,” says Arulrajah. “While we have never let his illness define him, and he remains a very positive and energetic boy, it was always on the back of his mind. We felt like we had exhausted all options for Daniel and still couldn’t get to the crux of the issue, and now we have. I was also so happy for the medical team because they have spent so long and probably many sleepless nights thinking about Daniel, trying to figure out what was wrong. When they told us, I could just tell this was a hugely important finding for them too.”

Through this discovery and international collaborations, a number of ARPC1B-deficient patients have been identified around the world. The SickKids team hopes their findings will lead to improved diagnosis and treatment for these patients. For example the treatment of choice for children with Wiskott-Aldrich syndrome is a bone marrow transplant, and the SickKids team is working to determine if this might also be a suitable treatment for patients with ARPC1B deficiency.

This study was supported by the Canadian Institutes of Health Research (CIHR), The Arthritis Society, Crohn’s and Colitis Canada, The Leona M. and Harry B. Helmsley Charitable Trust and SickKids Foundation. It is an example of how SickKids is contributing to making Ontario Healthier, Wealthier and Smarter.

Muise and Kahr are also Associate Professors in the Departments of Paediatrics and Biochemistry at the University of Toronto.

About The Hospital for Sick Children

The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized child and family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit Follow us on Twitter (@SickKidsNews) and Instagram (@SickKidsToronto).

Media contacts

Caitlin Johannesson
The Hospital for Sick Children
416-813-7654, ext. 201436

Matet Nebres
The Hospital for Sick Children

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