Toronto doctors identify new disease in children caused by defective gene

Toronto doctors identify new disease in children

TORONTO — Daniel Nevins-Selvadurai’s case had doctors at Toronto’s Hospital for Sick Children baffled. At age three, he had developed blood in his stool, a sign of possible hereditary inflammatory bowel disease. But testing for all the genetic mutations known to cause the condition came back negative.

As he grew older, Daniel’s symptoms became more diverse. He developed unusual rashes and painful lumps in his legs, as well as having an abnormally high white cell count and low platelets in his blood, pointing to an unidentified problem with his immune system.

A host of doctors at the hospital — among them specialists in blood disorders, cancer, rheumatology, immunology and gastroenterology — couldn’t pin down the cause of the child’s illness.

“Nobody could give us a diagnosis, so he was passed from one specialist to another over the years and various people did various tests,” said his mother, Christina Arulrajah. “He showed signs of so many different diseases.”

Still, Dr. Aleixo Muise, a gastroenterologist who had been seeing Daniel for his inflammatory bowel disease, or IBD, said that because of the boy’s wide-ranging symptoms “all the doctors thought that he must have a genetic cause to his disease.”

Then in 2014, a team led by Muise launched a project to explore the genetic basis of IBD, using an advanced technology for studying patients’ DNA. Daniel’s genome was among those investigated using a technique called whole-exome sequencing.

It was then that they had their eureka moment.

Testing of Daniel’s genome turned up a mutation never before seen. The defect was in a gene known as ARPC1B, which produces a protein the body’s cells need to change shape, move, divide and perform other vital functions.

His ARPC1B gene was expressing none of this critical protein.

“ARPC1B, we know, plays a very important role in the immune system and how different cells in the body — mostly found in the blood — work,” said Muise.

“Sometimes it’s surprising that one defect causes such widespread different types of disease in one patient, but this one mutation explains all the problems Daniel had.”

The Sick Kids team subsequently discovered two other patients who were related to each other but not to Daniel, who also had a mutation that left them with very little ARPC1B protein. Since then, about 20 children worldwide have been identified with the genetic mutation.

“It gave us enough evidence to know that this was a brand new disease that hadn’t been described before,” said Muise.

The discovery of what’s been dubbed ARPC1B syndrome is described in Monday’s edition of the journal Nature Communications.

“Daniel was over the moon to get a diagnosis,” said his mother. “When they found out what was wrong, it was a real relief. 

“In his mind, it’s all about the cure. Now that there’s a diagnosis, there’s now going to be a cure.”

His doctors believe a bone-marrow transplant will give Daniel new blood cells — including immune cells — that won’t carry the genetic mutation. A search is now on for an appropriate donor for the 10-year-old.

“If you do a bone-marrow transplant or you replace his immune system, this should cure him of his disease,” said Muise.

Daniel’s mother said she’s still trying to get her head around the notion of a cure after watching her son deal with so many health issues since infancy, the worst of which was seeing him repeatedly in pain.

“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,” Arulrajah said of her soccer-loving son.  

She hopes a successful bone-marrow transplant will mean an end to all the medications Daniel has had to take to treat his various symptoms over the years, including long courses of a steroid that have affected his growth.

“It would be absolutely fantastic.”

 

-Follow @SherylUbelacker on Twitter.

Sheryl Ubelacker, The Canadian Press

Canadian Press

Get local stories you won't find anywhere else right to your inbox.
Sign up here

Just Posted

West Kelowna’s Grizzli Winery to launch take-home floral creations workshop

The Workshop teaches the community to build creations such as table centerpieces and vase arrangements

Peachland resident finds severed bear paw on driveway

Tracie Gordon thought it was a Halloween prank, but it turned out to be a real bear paw

Kelowna RCMP investigating alleged group attack on teenager

A 14-year-old boy claims he was attacked by a group of teens Friday night

14th anniversary of Kelowna man’s sudden disappearance

Aaron Derbyshire was out with friends on Sept. 30, 2006, and hasn’t been seen since

105 new COVID-19 cases, 1 death as health officials urge B.C. to remember safety protocols

There are currently 1268 active cases, with 3,337 people under public health monitoring

Orange Shirt Day lessons of past in today’s classrooms

Phyllis Webstad, who attended St. Joseph’s Mission Residential School in British Columbia, is credited for creating the movement

Is it time to start thinking about greener ways to package cannabis?

Packaging suppliers are still figuring eco-friendly and affordable packaging options that fit the mandates of Cannabis Regulations

Greens’ Furstenau fires at NDP, Liberals on pandemic recovery, sales tax promise

She also criticized the NDP economic recovery plan, arguing it abandons the tourism industry

Join Black Press Media and Do Some Good

Pay it Forward program supports local businesses in their community giving

U.S. Presidential Debate Takeaways: An acrid tone from the opening minute

Here are key takeaways from the first of three scheduled presidential debates before Election Day on Nov. 3

B.C. nurses report rise in depression, anxiety, exhaustion due to pandemic

A new UBC study looks into how the COVID-19 response has impacted frontline nurses

National child-care plan could help Canada rebound from COVID-induced economic crisis: prof

A $2 billion investment this year could help parents during second wave of pandemic

Most Read