Daniel Nevins-Selvadurai was only four weeks old when his long and painful medical mystery began back in July 2006.
His mother, Christina Arulrajah, suspected he had the flu and took him to the doctor.
The visit quickly turned into an ambulance ride to Toronto's Hospital for Sick Children, where a doctor made a shocking diagnosis.
"I was told he had a stroke," Arulrajah said, "at which point I told the doctor, 'No, it's only old people who get strokes.' Sure enough they did an MRI and showed he had a stroke."
Daniel made a full recovery from the stroke but he soon became a frequent patient at SickKids with a weak immune system and a growing list of painful symptoms: stomach problems, blood in his stool, rashes and infections resulting in sepsis.
"They tested him for Crohn's disease, ulcerative colitis; it turned out not to be either," Arulrajah said.
'We are puzzled'
Years went by and his symptoms became more baffling. Daniel was referred to the hospital's clinical teams specializing in hematology, oncology, rheumatology, immunology, gastroenterology, dermatology and other fields.
The doctors did their best to ease his pain but couldn't provide answers.
"A lot of people saying, 'We are puzzled,'" the mother said. "We heard every synonym for the word medical mystery."
But in a paper published today in Nature Communications, a team of clinician-scientists from SickKids outline how they finally managed to solve the mystery of Daniel's illness using advanced DNA sequencing. The little boy's genome revealed a new disease caused by a never-before-seen gene mutation — one which might also explain the painful health problems of two more SickKids patients.
Dr. Aleixo Muise, a gastroenterologist and one of the leaders of the study, met Daniel seven years ago. In fact, the little boy was one of his first patients at the hospital.
He suspected Daniel had a genetic disorder but he recalls being frustrated because he couldn't figure out which one.
"So we tried to treat him the best as we could, using the drugs that were available, but we knew we were just putting a Band-Aid on his symptoms and not really treating his actual disease."
In late 2014, Muise and the SickKids team earned a grant for a study of inflammatory bowel disease and similar conditions that would involve sequencing the genomes of select patients. Muise quickly thought of Daniel and enrolled him in the study.
"The big game-changer for Daniel is that we were able to sequence his DNA and from that we were able to identify a mutation of a specific gene that explained all the symptoms that he had," Muise said.
Daniel's mutation was in ARPC1B, a gene that produces a core protein of the Arp2/3 complex, which cells need to change shape, divide and perform other important tasks.
When hematologist Dr. Walter Kahr studied Daniel's platelets, he noticed there was no ARPC1B protein. Doctors had previously assumed the protein was essential to survival.
The co-leader of the study says the ARPC1B protein deficiency explains why Daniel's platelets are small and misshapen. He says normal platelets, which are responsible for clotting blood, resemble fried eggs but Daniel's are spiky.
"It ... explains the fact that the patient had a lot of bleeding problems," he said. "When you have the inflammation, which is part of it, but also if the platelets don't work very well, there's a lot of bleeding. And this patient had a lot of bleeding issues."
Doctors at SickKids also discovered Daniel isn't their only patient with the disease. They found two other patients with the same mutation and about 20 more cases worldwide.
Daniel's doctors believe a bone marrow transplant could cure him and they're actively searching for a donor. The 10-year-old is excited about the possibility of putting his health problems behind him.
"It would be really nice because I wouldn't have to go to doctors constantly, it would just be a normal checkup."