A ten-year-old boy in Toronto, Canada has finally been diagnosed with a previously undiscovered genetic disorder that has plagued him with a myriad of symptoms his whole life.

Daniel Nevins-Selvadurai’s medical story began as a four-week-old, in July 2016. His mother, Christina Arulrajah, suspecting he had flu, took him to the doctor. However, the visit quickly turned into an ambulance ride to Toronto's Hospital for Sick Children.

“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.”

Patient had “signs of many different diseases”

Although Daniel made a full recovery, he soon became a frequent patient with a weak immune system and a growing list of painful symptoms: stomach problems, blood in his stool, rashes and infections resulting in sepsis.

Testing for all the genetic mutations known to cause the condition however came back negative. “They tested him for Crohn's disease, ulcerative colitis; it turned out not to be either,” Arulrajah said.

The patient’s symptoms became more diverse as he grew up. He developed unusual rashes and painful lumps in his legs, as well as an abnormally high white cell count and low platelets in his blood, pointing to an unidentified problem with his immune system.

According to the patient’s mother, for many years, Daniel was referred to numerous specialists within the hospital who could not diagnose him as “he showed signs of so many different diseases.”

Dr Aleixo Muise, a gastroenterologist at the hospital, suspected Daniel had a genetic disorder because of the wide-ranging symptoms but recalls being frustrated because he could not 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,” he said.

Genetic project identifies new mutation

In 2014, a team led by Muise launched a project to explore the genetic basis of irritable bowel syndrome, using whole-exome sequencing, with Daniel's genome among those investigated.

Daniel's genome revealed a mutation never seen before. The defect was in a gene known as ARPC1B, which produces a core protein of the Arp2/3 complex in cells, important for the cell to change shape, move, divide and perform other vital functions. The patient’s ARPC1B gene was expressing none of this critical protein.

The difference between a normal platelet and the platelet of someone with Daniel's protein deficiency. Photo credit: CBC News/Hospital for Sick Children
The difference between a normal platelet and the platelet of someone with Daniel's protein deficiency. Photo credit: CBC News/Hospital for Sick Children

Haematologist Dr Walter Kahr says the protein deficiency explains why Daniel's platelets are small and misshapen. Researchers previously assumed that the protein was essential for survival and that people “cannot live without ARPC1B protein”.

“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.”

20 children worldwide identified with the mutation

The 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, 20 children worldwide have been identified with the genetic mutation.

Daniel’s doctors believe a bone marrow transplant will give Daniel new blood cells that will not carry the genetic mutation.

“If you do a bone-marrow transplant or you replace his immune system, this should cure him of his disease,” said Muise.

“Daniel was over the moon to get a diagnosis,” said his mother. “In his mind, it's all about the cure. Now that there's a diagnosis, there's now going to be a cure.”

Patients with this mutation will now have a chance to be treated for the genetic disorder, such as Daniel who has had to take medication to treat his various symptoms over the years, including long courses of a steroid that have affected his growth. MIMS

Read more:
BPAN, the ‘one in a million’ genetic disorder
Gene editing saves a two-year-old girl from leukaemia
5 mysterious illnesses that doctors still cannot explain

Sources:
http://www.timescolonist.com/toronto-doctors-identify-new-disease-in-children-caused-by-defective-gene-1.13820920
http://www.cbc.ca/news/health/illness-sick-kids-hospital-genome-1.4053311
http://www.sickkids.ca/AboutSickKids/Newsroom/Past-News/2017/SickKids-team-identifies-new-disease-solves-medical-mystery.html