Toronto doctors identify new disease in children caused by defective gene – Medicine Hat News

By Sheryl Ubelacker, The Canadian Press on April 3, 2017.

TORONTO Daniel Nevins-Selvadurais case had doctors at Torontos 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, Daniels 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 couldnt pin down the cause of the childs 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 boys 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. Daniels genome was among those investigated using a technique called whole-exome sequencing.

It was then that they had their eureka moment.

Testing of Daniels genome turned up a mutation never before seen. The defect was in a gene known as ARPC1B, which produces a protein the bodys 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 its 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 hadnt been described before, said Muise.

The discovery of whats been dubbed ARPC1B syndrome is described in Mondays 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, its all about the cure. Now that theres a diagnosis, theres now going to be a cure.

His doctors believe a bone-marrow transplant will give Daniel new blood cells including immune cells that wont 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.

Daniels mother said shes 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.

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Toronto doctors identify new disease in children caused by defective gene - Medicine Hat News