New disease in children is identified

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 were 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 a 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.

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 wideranging 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.

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.

The Sick Kids team subsequently discovered two other patients 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.