Frequently Asked Questions
What is the purpose of this study?
The purpose of this study is to assess the benefits of whole exome/genome sequencing +/-mitochondrial DNA sequencing at the start of a patient’s work-up for an inborn error of metabolism. Some of the outcomes we will be assessing include: time to genetic results/diagnosis, time to treatment, changes in clinical management, impact on family planning and familial testing, cost-effectiveness, and quality of care/patient experiences.
Which patients are eligible for the study?
We are accepting patients of all ages. The inclusion criteria are:
- The patient is suspected to have an inborn error of metabolism (i.e., metabolic disorder), and
- The patient consents to a referral to the CPMN.
Patients can be referred to the study directly from their primary care provider (or any other clinician), whether or not they have already been referred to or seen by Genetics & Metabolism.
Since we are offering comprehensive DNA testing as a first-line test, patients whose signs/symptoms remain unsolved and could point to a variety of metabolic disorders are the best referrals for the CPMN. As examples, the types of patients in whom an inborn error of metabolism should be considered include those with:
- Recurrent, unexplained rhabdomyolysis with elevated CK
- Unexplained hepatosplenomegaly (especially if there are CNS signs and symptoms)
- Unexplained leukodystrophy
- Unexplained cardiomyopathy
- Unexplained movement disorders or dystonia
- Unexplained developmental regression or intractable seizures in children
How do I refer a patient to the study?
To refer a patient to the study, please click here. You can submit a web form, which will send the referral directly to our study team. Alternatively, you can also download and complete the fillable PDF form, then send it to our study team by fax (204-789-3907).
What happens after my patient is referred to the study?
Our study team will review your referral. If the patient is likely eligible (i.e., likely to have an inborn error of metabolism), a member of the study team will call your patient and arrange a meeting to obtain informed consent.
After a patient consents to the study, we will review their case with metabolic/genetic specialists at our weekly triage meeting to determine whether “OMICS First” testing through the CPMN (i.e., whole exome/genome sequencing +/- mitochondrial DNA sequencing) should be pursued; you and your team will also be invited to attend this meeting.
We will collect buccal samples from patients who qualify for “OMICS First” testing through the CPMN. Once the samples arrive at the lab, results will take about 2 weeks. The study team will have regular
variant meetings to review genetic test results; you and your team will be invited to attend the meeting to discuss your patient’s results. Following this meeting, we may arrange an appointment to disclose the results to your patient and discuss next steps in their clinical care, or we may ask that you share the results with your patient.
What happens if the study finds a diagnosis for my patient?
We will disclose the results to your patient and discuss next steps in their clinical care. We will refer all study patients to the Program of Genetics & Metabolism (if not already done). Because the results of DNA testing can be worrisome or stressful, patients will have access to a CPMN genetic counsellor.
You will receive a copy of the genetic test report for your patient. We will also communicate clinical recommendations and next steps to you.
Will you return incidental findings?
Incidental findings (IFs) are unexpected disease-causing variants unrelated to the reason for referral/testing. The genetic testing offered through our study is targeted to each patient’s phenotype; therefore, we will not purposely search for IFs. However, we still anticipate that IFs will be discovered in a minority of participants.
We will only return medically actionable IFs, meaning IFs with a relatively high risk of causing disease where screening/prevention/treatment options are available. Return of medically actionable IFs will follow the Canadian College of Medical Geneticists 2015 Position Statement, and as such, will be handled differently in children, dependent adults, and competent adults:
- Children: We will report pathogenic IFs for medically-actionable disorders that can be childhood-onset (e.g., Neurofibromatosis 1 or Long QT syndrome). We will not disclose exclusively adult-onset IFs in children unless we strongly believe it is in the child’s or family’s best interest.
- Dependent adults: We will report medically actionable IFs to the legal substitute decision-maker who provided consent for study participation. This is in the best interest of the patient, as it ensures that they have the opportunity to receive appropriate healthcare and take preventative actions to reduce harms related to the IF.
- Competent adults: Adults who are able to make their own decisions have the option of whether or not they wish to be informed of medically actionable IFs.
How long will it take to get results?
Results will be available approximately 2 weeks after your patient’s sample arrives in the lab in Calgary. We will then review the results at one of our regular variant meetings. You and your team will be invited to attend the variant meeting, should you wish. Following the meeting, we may arrange an appointment to disclose the results to your patient and discuss next steps in their clinical care, or we may ask that you share the results with your patient.
What happens if no disease-causing variants are found through the study?
You will receive a copy of the genetic test report for your patient. We will also communicate recommendations and possible next steps to you. We may arrange an appointment to disclose the results to your patient and discuss next steps in their clinical care, or we may ask that you share the results with your patient.
We will refer all study patients to the Program of Genetics & Metabolism (if not already done), regardless of their genetic test results.
What happens if my patient is not eligible for genetic testing through the CPMN study?
In some cases, a patient may be deemed ineligible for the “OMICS First” approach offered through the CPMN. Possible reasons for ineligibility may be:
- The patient’s features are not strongly suggestive of an inborn error of metabolism
- A single-gene/multi-gene panel is more appropriate than whole exome/genome sequencing (e.g., the patient has a positive newborn screen, known family history of a genetic/metabolic disease, or signs/symptoms that are strongly suggestive of a specific metabolic condition)
Patients who are deemed ineligible for genetic testing through the CPMN will be included in the CPMN database for our statistical analyses (as explained to patients during the consent process). We will ensure that all patients referred to the CPMN are also referred to the Program of Genetics & Metabolism (if not already done).
What if my patient wants to withdraw from the study?
Patients are free to withdraw from the study at any time. This will not impact their medical care in the local Metabolics program. Patients may also request that their DNA sample be returned to them or destroyed at any time.
If your patient would like to withdraw from the study or have their sample returned/destroyed, please ask them to contact the study team directly.