Toronto boy's DNA reveals mysterious new disease and possible cure

DanielNevins-Selvaduraiwas only four weeks old when his long and painful medical mystery began back in July 2006.

His mother, ChristinaArulrajah, 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 hada stroke,"Arulrajahsaid, "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 hada stroke."

Daniel made a full recovery from the stroke but he soon became a frequent patient atSickKidswith 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 forCrohn'sdisease, ulcerative colitis; it turned out not to be either,"Arulrajahsaid.

'We are puzzled'

Years went by and his symptoms became more baffling. Danielwas referred to the hospital's clinical teams specializinginhematology, 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 fromSickKidsoutline 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 moreSickKidspatients.

Dr.AleixoMuise, agastroenterologistand 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,Muiseand theSickKidsteamearned a grant for a study of inflammatory bowel disease and similar conditionsthat would involve sequencing the genomes of selectpatients.Muisequickly 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,"Muisesaid.

Protein deficiency

Daniel's mutation was inARPC1B, a gene that produces a core protein of theArp2/3 complex, which cells need to change shape, divide and perform other important tasks.

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WhenhematologistDr. WalterKahrstudied Daniel's platelets, he noticed there was noARPC1Bprotein. Doctors had previously assumed the protein was essential to survival.

The co-leader of the study says theARPC1Bprotein deficiency explains why Daniel'splateletsare small and misshapen. He says normal platelets, which are responsible for clotting blood, resemblefried eggs butDaniel'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 atSickKidsalso discovered Danielisn'ttheir 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."