"All For One" Project Offers Hope for One of Health Science’s most Challenging Groups of Genetic Conditions
April 26, 2022
For many years, Alex (not their real name) sought answers to an illness that could not be identified.
Alex’s symptoms involved the muscles and pointed to a number of different hereditary metabolic conditions known as Inborn Errors of Metabolism (also commonly referred to as IEM). The conditions affect the body’s ability to convert fat, protein, or sugars into energy.
While individually, these are rare disorders, they are collectively common (a British Columbia study estimated about 40 per 100,000 people are born with an IEM). The health effects can be serious. Some IEM-diagnosed patients experience relatively mild symptoms such as skin rashes and various aches and pains, others endure (to name a few) more serious long-term health issues, including muscle weakness, strokes, deafness, and internal organ failure.
Alex’s symptoms were similar to other close family members, including Alex’s mother and brother.
“My brother has symptoms identical to what my mother lived with 38 years ago. She is not with us anymore, but I am reliving it all, watching my brother go down the exact path my mother did.”
Recently, Alex sought answers at the Canadian Prairie Metabolic Network (CPMN) - its main site in Winnipeg at the Children’s Hospital Research Institute of Manitoba at the Bannatyne campus (University of Manitoba). The CPMN is offering patients like Alex hope to better understand the cause of one of health science’s most challenging and puzzling genetic conditions.
“It was a simple DNA cheek swab test that yielded results in a very short time. The research team made sure to answer all my questions and kept me informed along the way,” said Alex.
The roots of the CPMN project began in 2018 when Genome Canada launched All For One, an initiative focused on providing precision health options to Canadians affected by a serious genetic condition. Following consultations with health and research stakeholders, the CPMN was formed as one of six Canadian regional projects. With $2.1 million in funding from the Canadian Ministry of Innovation, Science and Industry, and Genome Canada support, the CPMN project partners also include Discovery DNA, Inc., Shared Health Manitoba, Genome Alberta, and Genome Prairie.
The CPMN offers a unique model that combines laboratory and clinical facilities to help diagnose, treat and conduct follow-up with patients with suspected IEMs. With Dr. Cheryl Rockman-Greenberg as its project leader and Angela Krutish as project manager, the CPMN’s focus on IEMs coincides with increasing interest in these conditions within the health science field.
“Over the years, we’ve seen a steady rise in IEM patient referrals,” said Krutish. “Along with the rise in cases, we’ve also seen an increase in the capabilities of the genetic technology that’s available. The CPMN offered a potential solution to meet the needs of patients with suspected IEMs.”
IEMs are a tricky group of genetic conditions because they can be tough to diagnose. IEM symptoms can emerge days, years, or even decades after birth. Common early symptoms, such as vomiting and diarrhea, are sometimes misidentified as they overlap with the signs and symptoms of much more common disorders, such as stomach flu. Spotting IEM is even more difficult in young patients, especially newborns.
“The signs and symptoms of IEMs are very nonspecific, which means many patients who have an IEM are never appropriately investigated,” said Dr. Greenberg. “When IEMs aren’t considered, and the patient is not referred, it creates long delays in diagnosis.”
For Greenberg, a research scientist at the Children’s Hospital Research Institute of Manitoba, her lead role with the CPMN marks another milestone in a career focused on pediatric care and genetics research. Her devotion has earned her national accolades, including an appointment as an Officer to the Order of Canada in 2019.
“I’ve worked in metabolics for what is it? 40 – no, 43 years!” said Greenberg, who earned her medical degree from McGill University. “I’ve always been involved in research and working on genetic and metabolic problems, including conditions that are overrepresented in certain populations.”
Greenberg noted one of the most immediate beneficial effects of the work done by the CPMN is building genomic testing capacity in the Prairie region while offering patients the possibility of precisely identifying a genetic condition.
“One of our greatest impacts is changing the course for patients with suspected metabolic problems who’ve had a long diagnostic odyssey and have been referred to the CPMN, where we’re offering a DNA test and next-generation sequencing.”
“We especially hope to focus on patients who are early in their diagnostic journey, where we can hopefully help them avoid undergoing many other tests.”
The CPMN uses an “OMICS-first” approach, which allows patients to go directly to genetics testing.
“With an OMICS-first approach, we’re going straight to genomic testing instead of the traditional approach to diagnosis,” said Krutish. “Traditionally, a patient would be tested for an IEM through blood or urine analysis, and from there, they might undergo genetic testing.”
“The OMICS-First approach is also more comprehensive. Instead of looking at just a single gene or a group of genes, with OMICS-First, all 20,000 genes in a patient’s body are examined.”
The comprehensive genomics approach to diagnosis also means greater levels of interaction between metabolic health care providers and researchers.
“We tend to approach this work in our own silos, where we have researchers doing their thing and clinicians doing their thing - but not a lot of communication or interaction between the two,” said Krutish. “Traditionally, genetic researchers and clinicians don’t talk to each other, but we have clinicians actively involved in submitting cases directly to researchers.”
“The CPMN is an environment where these groups work together. This is important because it helps build a clinical network which speeds up the diagnostic process.”
The speed of the CPMN model, Krutish noted, is also reflected by where the tests are done. “The CPMN offers patients a clinical test through an accredited Canadian laboratory called Discovery DNA, Inc. The results we get back don’t need to be confirmed by another lab, so testing and diagnosis are much faster than in many research studies.”
While the CPMN is in the early stages of diagnosing patients (it began patient intake in November 2021), Greenberg noted the results have already been highly encouraging.
“The project is going extremely well so far. It’s improving access to care in Prairie centres, and we’ve also raised awareness about IEM and the OMICS-First approach,” said Greenberg.
“What’s especially important is that we’re learning, even in the first few months of the project, the direct impacts of being able to offer genomic sequencing as a first test for patients who are worried that they might have an IEM.”
“What I’ve heard over and over again from patients is how glad they are to participate in an innovative project that might help them to find answers if they’re wondering if they have a genetic disorder or to rule out genetic disorders.”
For many who suspect they have an IEM, the process from diagnosis to treatment can be lengthy. Greenberg noted the CPMN model could have a significant long-term effect on building regional capacity in the Prairies and expanding precision health services to Canadians.
“I think an overarching theme is that there are clinical needs as things are advancing so quickly in metabolic genomics. It’s important to have a clinical network across the prairies. There is incredible value in having a clinical team in Manitoba, Saskatchewan, and Alberta, working together for the betterment of patient care.”
While not always producing a definitive diagnosis, Greenberg said that CPMN patients discover a sense of relief by having access to advanced genetic testing.
“People appreciate the attempt to make a diagnosis and to actually be heard,” said Greenberg.
“What CPMN is showing is that even though for some patients we might not make a diagnosis, they appreciate that someone is trying to help them. We let patients know that this is the beginning, that we’re not going to forget about them, and that we’re going to continue with follow-up.”
While the genomic sequencing did not reveal the metabolic diagnosis, the result, while not pinpointing Alex’s condition, still brought peace of mind.
“The testing was way more advanced than I could understand, but in any case, my results were the best-case scenario. There was not enough significant evidence for genetics to pursue any more testing.”
“This has brought me relief!,” said Alex, who still thinks about how the CPMN might have helped Alex’s brother.
“It makes me think, what if this would have been an option for him? I can’t imagine how much time and cost savings to our health care system this could be, but more importantly, how much stress this would have eliminated for him and any other patients waiting months on end for each test result to come in. Then only to start all over again with the next round of tests. This is where frustration sets in.”
“My story will continue as I search for the answers to my symptoms. I really hope the CPMN will help others to get the answers they are looking for. There is nothing easy waiting for test results of any kind,” said Alex.
Even when the result isn’t always positive, simply being there for patients is a sentiment not lost on Greenberg.
“I always think of Maya Angelou who is quoted for having said ‘I’ve learned that people will forget what you said, people will forget what you did, but people will never forget how you made them feel’”.
This is the first article profiling the Canadian Prairie Metabolic Network, funded in part by Genome Canada and supported by Genome Prairie. Future articles will examine the continued progress of the network and its successes in building capacity and providing precision heath to Canadians in the prairie region and beyond.