What are genes?

Our bodies are made up of many cells. Each of our cells has DNA, which acts as the instruction manual for our bodies. Our DNA is made up of a string of letters called the genetic alphabet, and these letters are broken up into the words (called genes) of the instruction manual. We have two copies of most of our genes – one copy from each of our biological parents. Spelling changes in our genes (also called variants or “mutations”) can cause the gene not to work properly, causing a genetic condition.

What is an “inborn error of metabolism” (IEM)?

An “inborn error of metabolism” or “metabolic disorder” is an inherited condition. It affects the way the body breaks down food, makes energy, and uses energy. An inborn error of metabolism can sometimes be diagnosed with DNA testing. Other times, it may be diagnosed with tests that look at the body’s chemistry and how energy is made/used.

What is the purpose of this study?

We want to find out if there are benefits to having non-genetics specialists request DNA testing early in the diagnostic work-up (also known as “mainstreaming” of the “OMICS First” approach) when someone is thought to have an “inborn error of metabolism” or other rare genetic condition.

Who can join this study?

This study is for children and adults. You may be eligible to join the study if:

• You have health problems that may be caused by an “inborn error of metabolism” or other rare genetic condition
• The cause of your health problems has not yet been found

What are the steps to join this study?

You must be referred to the study by a non-genetics health care specialist. As examples, this could be a neurologist, nephrologist, developmental pediatrician, or other specialist.

A member of the study team will call you to give you more information. If you decide to join the study, you will be asked to sign a consent form.

If my doctor refers me to the study, what happens next?

You will meet with a member of the study team. This meeting can be in-person, over the phone, or by video call. They will explain the steps of the study and possible benefits and harms of joining; they will also answer any questions you have. To officially join the study, you must sign a consent form.

After consenting to the study, we will review your medical history and any tests you already had at our “OMICS First” Committee meeting. The committee will decide whether you qualify for the “OMICS First” DNA testing. If you qualify for this DNA testing, it will be done from a blood draw or DNA stored in our local laboratory. If you do not qualify for the DNA testing, you can still be a part of the study.

If I am referred to the study, do I have to join?

No, joining the study is voluntary. This means you can make your own decision about whether to join the study or not, and you do not have to join if you do not want to. You can also stop being part of the study at any time. If you decide not to join the study or you want to leave the study at any time, this will not affect your medical care.

If I join the study, what will happen to my DNA sample?

After your blood sample has been collected, it will be sent to the Shared Health Genomics Laboratory in Winnipeg’s Health Sciences Centre. In the laboratory, the DNA will be isolated from your blood sample, and DNA testing will be performed. Because Shared Health Genomics Laboratory is a certified laboratory, your sample will include all the information that identifies you (such as name and date of birth).

You are the owner of your DNA, and it is considered to be “on loan” to us for the purpose of this research study. The DNA from your blood sample will only be used for this study. The lab and our study team will not sell your DNA, will not use your DNA to make money, and will not share your DNA or results with others without your permission.

At the beginning of the MGM study, Shared Health Genomics Laboratory was confirming their DNA testing process. During this confirmation time, DNA samples were also sent to a certified laboratory in Toronto called SickKids Genome Diagnostic Laboratory. This confirmation period is now complete, and all samples will only be sent to the Shared Health Genomics Laboratory.

How can I learn more about the DNA testing in this study?

Our study team will be happy to explain the steps of the study and the DNA testing that might be done. You can also check the Resources page here.

What is the chance that this study will find an answer for my health problems?

We think that the DNA testing in this study will find the cause of someone’s health problems (i.e., find a diagnosis) about 30% of the time.

How long will it take to get results?

We expect it will take 4-6 months to get a result once your sample arrives at the DNA lab. The lab will send the results to our study team. We will set up a meeting with your health care provider or with yourself to explain your results as soon as we are able.

Who will my information be shared with if I join this study?

Your DNA sample and information that identifies you will be sent to the Shared Health Genomics Laboratory. The study team will also give the lab information about your health problems because this will help the lab to interpret your DNA results. This data will be stored in locations under the exclusive control of Shared Health Genomics and will follow all their requirements for safely storing patient data.

At the beginning of the MGM study, Shared Health Genomics Laboratory was confirming their DNA testing process. During this confirmation time, DNA samples were also sent to a certified laboratory in Toronto called SickKids Genome Diagnostic Laboratory. This confirmation period is now complete, and all samples will only be sent to the Shared Health Genomics Laboratory.

What are the possible benefits of joining this study?

It is possible (but not guaranteed) that DNA testing will find the cause of your health problems (i.e., find a diagnosis). This information might:

• Change your medical care
• Allow you and your family to access certain resources
• Help you, your family, and your health care providers understand your health problems better
• Tell you the chance that your relatives will have the same health problems

We also hope the information learned from this study will help other people in the future who are thought to have an inborn error of metabolism or other rare genetic condition.

What are the possible harms of participating in this study?

The DNA testing in this study may find the cause of your health problems. This information might cause worry or stress. For some people, this information might affect their decision to have a child, or it might affect other lifestyle decisions. Because inborn errors of metabolisms can be inherited, the information might also impact other members of your family.

Sometimes, DNA testing finds other gene changes (called “variants”) that are not related to the reason a person was referred to the study. These gene changes might mean that you are at-risk for or will have other health problems in the future.

Because the results of DNA testing can be worrisome or stressful, you will have access to a genetic counsellor. Genetic counselling helps patients/families assess the pros and cons of DNA testing, as well as cope with the results. This support will be available through the MGM team and through the Shared Health Program of Genetics & Metabolism.

What is the purpose of this study?

We want to validate a new workflow that would offer additional research tests (or “OMICS” modalities) to people for whom DNA testing did not find a diagnosis.

Who can join this study?

This study is for children and adults. You may be eligible to join the study if:

• You have health problems that may be caused by an inborn error of metabolism or other rare genetic condition
• You had a DNA test that came back negative or with uncertain results

What are the steps to join this study?

You may be referred to the study by your health care specialist. As examples, this could be a geneticist, neurologist, nephrologist, or other specialist.

The study team will review the information provided by your specialist, and if you are eligible for one of the “Multi-OMICS” tests being offered and you decide to join the study, you will be asked to sign a consent form.

If my doctor refers me to the study, what happens next?

The study team will review the information provided by your specialist and determine if we can offer further testing to help understand your DNA test results. You will then meet with a member of the study team. This meeting can be in-person, over the phone, or by video call. They will explain the steps of the study and possible benefits and harms of joining; they will also answer any questions you have. To officially join the study, you must sign a consent form.

If I am referred to the study, do I have to join?

No, joining the study is voluntary. This means you can make your own decision about whether to join the study or not, and you do not have to join if you do not want to. You can also stop being part of the study at any time. If you decide not to join the study or you want to leave the study at any time, this will not affect your medical care.

Do I need to give another blood sample?

The kind of sample needed for “Multi-OMICS” tests will depend on your previous results. For some tests we will not need a new sample at all. For other tests, we may need:

• A blood sample
• A urine sample
• A 3 mm skin sample collected under local anesthetic

If I join the study, what will happen to my sample?

After your sample has been collected, it will be sent to the researcher running the test. Your sample will be labeled with a study ID number. It will not have any identifying information about you (such as name or date or birth).

You are the owner of your DNA or other tissue sample, and it is considered to be “on loan” to us for the purpose of this research study. The DNA from your sample will only be used for this study. The study team will not sell your DNA, will not use your DNA to make money, and will not share your DNA or results with others without your permission.

What kind of “Multi-OMICS” test could be offered?

There are many different “Multi-OMICS” tests that might be helpful to clarify your test results. Based on the information provided by your specialist, the study team will determine which one makes the most sense for you. Our study team will explain the test option(s) to you in detail before you make a decision.

What is the chance that this study will find an answer for my health problems?

It is uncertain whether a “Multi-OMICS” approach will provide more information about your health problems. Regardless, all results will be shared with you.

How long will it take to get results?

Since these are research studies, results may take up to 1 year.

Who will my information be shared with if I join this study?

We will provide the researcher running the test your biological sex, your age, your health problems, the age your health problems started, and your previous DNA test results. Researchers will not be given your name, date of birth, or healthcare numbers.

What are the possible benefits of joining this study?

It is possible (but not guaranteed) that this testing will confirm or find the cause of your health problems (i.e., a diagnosis). This information might:

• Help you, your family, and your health care providers understand your health problems better
• Tell you the chance that your relatives will have the same health problems

It is not likely that this study will change your or your family member’s medical management or treatment.

We also hope the information learned from this study will help other people in the future who are thought to have an inborn error of metabolism.

What are the possible harms of participating in this study?

The testing in this study may or may not find the cause of your health problems. If you are asked to provide an additional sample (such as blood or skin) the risks and benefits will be explained to you. For some people, finding or confirming a diagnosis through a “Multi-OMICS” study may be helpful, while for others this information may cause worry or stress. Alternatively, not finding a reason for your health problems may be disappointing. Because inborn errors of metabolism can be inherited, the information might also impact other members of your family.