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

Just Posted

College buys a yurt to boost student success

Round tent-like structure part of college instructional shift

Soup kitchen sees “groundswell of community support”

Donations toward looming tax bill push non-profit back in the black

Terrace husband and wife honoured for saving each other’s lives

BC Ambulance presented each a Vital Link Award for separate incidents of CPR

Council supports lobby for fair share of cannabis tax revenue

The City of Terrace is throwing its support behind a West Kelowna… Continue reading

Airport registers modest passenger increase

Manager anticipates further growth in 2018 as expansion project nears completion

Airport registers modest passenger increase

Manager anticipates further growth in 2018 as expansion project nears completion

Two Canadians, two Americans abducted in Nigeria are freed

Kidnapping for ransom is common in Nigeria, especially on the Kaduna to Abuja highway

Are you ready for some wrestling? WWE’s ‘Raw’ marks 25 years

WWE flagship show is set to mark its 25th anniversary on Monday

B.C. woman who forged husband’s will gets house arrest

Princeton Judge says Odelle Simmons did not benefit from her crime

Women’s movement has come a long way since march on Washington: Activists

Vancouver one of several cities hosting event on anniversary of historic Women’s March on Washington

Liberals’ 2-year infrastructure plan set to take 5: documents

Government says 793 projects totalling $1.8 billion in federal funds have been granted extensions

Workers shouldn’t be used as ‘pawns’ in minimum wage fight: Wynne

Comments from Kathleen Wynne after demonstrators rallied outside Tim Hortons locations across Canada

John ‘Chick’ Webster, believed to be oldest living former NHL player, dies

Webster died Thursday at his home in Mattawa, Ont., where he had resided since 1969

World’s fastest log car made in B.C. sells for $350,000 US

Cedar Rocket auctioned off three times at Barrett-Jackson Co., netting $350,000 US for veterans

Most Read