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Children with rare and complex immune system disorders now have a much better chance of getting a rapid, accurate diagnosis thanks to a clinical research group at the University of Calgary’s Cumming School of Medicine (CSM) and the Alberta Children’s Hospital (ACH). The brings together clinicians and researchers from various specialties to help solve the medical mysteries these children present.

The program is the brainchild of Dr. Ashish Marwaha, MD, PhD, a member of the Alberta Children’s Hospital Research Institute (ACHRI) and a medical genetics physician at ACH. His commitment to innovative solutions has led to dozens of children with rare disorders being seen by a cohort of geneticists, immunologists, dermatologists and rheumatologists.

“Often when I see the families in clinic they say they are relieved to have someone sit and listen to their story from start to finish,” Marwaha says.

“They know something is wrong. To have us take them seriously and start investigations makes them feel they are finally in the right place, rather than hopping around to different doctors to be told something different or get no answer at all.”

As part of the program, Marwaha co-leads monthly clinical rounds alongside Dr. Marinka Twilt, MD, MSCE, PhD, ACHRI member and paediatric rheumatologist at ACH, to discuss patient cases and the tests that could be ordered for them. Since he started the group, he’s received 166 referrals. Marwaha says the high number of referrals is related to the tenfold increase in the number of immune-related disorders over the past few decades.

“We started with around 50 conditions in the '80s or '90s and it’s ballooned to more than 500 now, making diagnosis all the more challenging.”

One such case was that of four-year-old Anaisha. In June 2021, she stayed in hospital for over a month with a high fever, weakness and pain in her feet, limiting her ability to stand and walk. Countless consults with medical specialists and tests could not determine the cause, until Marwaha and his group took on her case.

Through genetic testing, they discovered she has adenosine deaminase 2, a systemic autoinflammatory disorder. She is one of only 500 people in the world with this condition.

“After weeks of not knowing, you get this call to say, ‘We have an answer for you,’” recalls Anaisha’s mom, Apoorva Vajpayee. “The diagnosis is hard to hear but it gives your family a path forward. It gives you hope.”

As a result of the diagnosis, Anaisha received precision therapy that helped resolve the inflammation and prevent her from having complications related to the condition in the future. She is now able to live as a healthy four-year-old thanks to the investigations of the complex immune dysregulation program.

Marwaha’s research into cases like Anaisha’s illustrates the collaborative work undertaken at the University of Calgary as a recipient of the prestigious One Child Every Child initiative. It falls under one of the grant’s three areas of greatest need — Precision Health and Wellness. The research team for this area is being led by Dr. Francois Bernier, MD, Marwaha’s colleague and mentor, and the scientific director of precision health for ACHRI.

“Bringing diverse experts together — including specialists from around the globe — combined with decades of investments in genomic medicine by the Alberta Children’s Hospital Foundation, we are able to get answers for critically ill children,” says Bernier.

One Child Every Child supports research aimed at ensuring ALL Canadian children are among “the healthiest, most empowered and thriving in the world.”

“The grant will enable us to think about how we provide care both on the research side and clinical side for newcomers and different populations,” Marwaha says.

“Anaisha’s family told me it was very difficult to be in this country without any familial support and have a child with a new diagnosis that they were trying to understand. It was an extra layer they were undergoing that other children and families wouldn’t experience that we were able to help mitigate through our commitment to helping their daughter.”

Marwaha’s work has garnered attention from hospitals across the country who regularly ask him to speak about his successes and challenges and offer guidance on best practices.

“We want Calgary to be a leader in the field of diagnostics, especially in immune disorders,” he says. “We have all the expertise here now in genetics. We hope to form bigger cohorts of specialists from hospitals and universities across the country. After all, in rare diseases, it's always beneficial to have more people you can call for help.”

Forming these connections will not only bring more expertise to the table but will also lay the groundwork for staging multi-centre clinical studies, enabling Calgary to transform child health research in Canada.

“I think it will give us a lot of opportunities to accelerate the care of all the children we see in the hospital and beyond.”