Commonly Asked Questions

• What is a mitochondrion?
• What is a mitochondrial disease?
• Why is Mayo Clinic starting the Mitochondrial Disease Biobank?
• Why would someone want to participate in the Mitochondrial Disease Biobank?
• Will participants of the biobank personally benefit?
• Will I find out if researchers discover anything about my health?
• What is the cost to participants?
• How long will Mayo Clinic use the Mitochondrial Disease Biobank?
• Who is eligible for the Mitochondrial Disease Biobank?
• How are participants chosen?
• Can I volunteer for the Mitochondrial Disease Biobank?
• What will be expected of me if I participate?
• Are there any risks of participation?
• How are samples and information stored?
• How will researchers access participants information?
• How is the Mayo Clinic Mitochondrial Disease Biobank funded?

What is a mitochondrion?

A mitochondrion (pleural-mitochondria) is a cellular structure, also called an organelle, which primarily produces energy for the cell in the form of ATP. The number of mitochondria per cell varies greatly by tissue type, but can be as great as 4000. Most DNA within a cell is contained in chromosomes; however mitochondria have their own distinct DNA, called mitochondrial DNA (or mtDNA). Mitochondrial DNA contains 37 genes, all essential for normal mitochondrial function.

What is a mitochondrial disease?

A mitochondrial disease is the result of the failure of mitochondria to complete its primary function, to provide energy to the cell. There are many different mitochondrial diseases within the group of disorders. Mitochondrial disorders primarily affect children, however more is now known about adult-onset disease. Mitochondrial disease leads to cell injury and even death. Symptoms of the disease can be mild to fatal and usually depend on which cells are affected. Common symptoms can include, but are not limited to: muscle weakness, gastrointestinal disorders, neurological problems like seizure, cardiac, liver or respiratory disease, developmental delay, poor growth or increased susceptibility to infection.

Why is Mayo Clinic starting the Mitochondrial Disease Biobank?

Having a biobank will make it much easier to conduct research studies about mitochondrial diseases because researchers will have access to blood and tissue samples, along with patient data, from hundreds of people all in one place.

Why would someone want to participate in the Mitochondrial Disease Biobank?

This study will not make participants' health better. It is for the benefit of research. The Mitochondrial Disease Biobank will serve as a resource that researchers can contact for specimens to be used for research studies. They may learn new information after examining the samples and information in the biobank. When that happens, they will share the information with other scientists and doctors. As a result, medical care for patients with mitochondrial diseases may improve; however, there is no guarantee this will benefit a specific patient or individual. Participants will not be paid for taking part in this study.

Will participants of the biobank personally benefit?

No. This study will not make participants health better. It is for the benefit of research. The Mitochondrial Disease Biobank will serve as a resource that researchers can contact for specimens to be used for research studies. They may learn new information after examining the samples and information in the biobank. When that happens, they will share the information with other scientists and doctors. As a result, medical care for patients with mitochondrial diseases may improve, however, there is no guarantee this will benefit a specific patient or individual. Participants will not be paid for taking part in this study.

Will I find out if researchers discover anything about my health?

No. The Mitochondrial Disease Biobank will not be releasing information learned through research studies to participants. They will share the information with other scientists and doctors. As a result, medical care for patients with mitochondrial diseases may improve; however, there is no guarantee this will benefit a specific patient or individual.

What is the cost to participants?

Participants will not need to pay for tests and procedures that are done just for this research study, including blood draw. However, participants and/or their health plan will need to pay for all other tests and procedures that they would normally have as part of their regular clinical care.

How long will Mayo Clinic use the Mitochondrial Disease Biobank?

Participants will be in the study for several years, as samples donated to the Mitochondrial Disease Biobank will serve as a research community resource until they are used up. By participating, individuals are agreeing to be a part of ongoing mitochondrial disease research. Participants have a right to leave the Mitochondrial Disease Biobank project at any time.

Who is eligible for the Mitochondrial Disease Biobank?

• Individuals age birth-100 years, male or female, any race/ethnicity.
• Potential participant shall have a suspected diagnosis of a mitochondrial disease based on a review of clinical history by a Mitochondrial Disease Biobank working group member using the following clinical criteria listed in the table below.
• Participants may also be a 1st-degree relative of a potential participant with a suspected diagnosis of a mitochondrial disease who wishes to also participate.
• Selected participants shall have at least two documented conditions contained within the minor clinical criteria (see table below), or one condition in the major criteria with evidence of a condition in the minor criteria, will be considered for inclusion of a participant of appropriate age.

	Major Criteria	Minor Criteria
Clinical	Multi-systemic symptoms characteristic of mito disorder Progressive clinical course with episodes of exacerbation A family history strongly indicative of an mtDNA mutation Exclusion of other metabolic or non-metabolic disorders	Symptoms compatible with a mitochondrial defect
Histology	>2% ragged red fibers (RRF) in skeletal muscle	Smaller numbers of RRF or widespread electron microscopy abnormalities of mitochondria
Enzymology	Cytochrome c oxidase negative fibers (>2-5%) or residual activity of a mito complex <20% in a tissue; <30% in a cell line, or <30% in >2 tissues	Antibody-based demonstration of an mito defect or residual activity of an mito complex 20%–30% in a tissue, 30%–40% in a cell line, or 30%–40% in >2 tissues
Functional	Fibroblast ATP synthesis rates >3 SD below mean	Fibroblast ATP synthesis rates 2–3 SD below mean, or fibroblasts unable to grow in galactose media
Molecular	Nuclear or mtDNA mutation of undisputed pathogenicity	Nuclear or mtDNA mutation of probable pathogenicity
Metabolic		One or more metabolic indicators of impaired metabolic function

• In addition, samples from patients with one of the following mitochondrial disease diagnosis will be included: Alpers' progressive sclerosing poliodystrophy, Barth syndrome, CPEO, Dominant optic atrophy, Friedreich's Ataxia, Hereditary paraganglioma, Hereditary spastic paraplegia, Kearns-Sayre syndrome, Leber hereditary optic neuroretinopathy, Leigh and Leigh-like Syndrome, MELAS, MERRF, NARP, Pearson syndrome, and Wolfram syndrome.

Exclusion Criteria

• Individuals who are unable or unwilling to provide informed consent.
• Individuals unwilling to consent to providing biospecimens to be stored in the biobank for an indefinite amount of time and to be used in future research studies of as yet unknown design.
• Individuals who do not have clinical symptoms that are indicative of a potential mitochondrial disease as determined by a chart review by at least one Mitochondrial Disease Biobank working-group member.
• Individuals who do not have a diagnosis of a mitochondrial disease.

How are participants chosen?

Potential participants may be identified by a Mayo Clinic care provider if they are being seen at the clinic. Participants may also be identified by a member of the Mayo Clinic Biochemical Genetics Laboratory staff, if a clinical sample is sent for testing. Lastly, individuals may volunteer to participate without any prior contact with Mayo Clinic.

Can I volunteer for the Mitochondrial Disease Biobank?

Yes. Individuals who meet eligibility criteria may volunteer for the biobank.

What will be expected of me if I participate?

Participants will be asked to:

1. Provide a sample of blood, if possible.
   1. Adult (18 years or age and over): 26.5 mL (about 3 tablespoons) of blood in 4 tubes.
   2. Adolescent (13-17 yrs): 16.5 mL (about 2 tablespoons) of blood in 3 tubes.
   3. Pediatric (birth through age 12): 6 mL (about 1 tablespoon) of blood in 2 tubes.
2. Provide researchers access to clinical waste tissue or post-mortem tissue, if available.

   Often individuals with a known or suspected mitochondrial disease have residual clinical samples (such as skin or muscle biopsy, urine, etc) stored for additional testing. If these samples are no longer needed and remain available, they can be located and collected for this study.

3. Complete a short questionnaire about themselves and their family.

   This questionnaire will ask participants age, sex, and known or suspected mitochondrial disorder. It will also ask a few questions about family members' health. This will take less than five minutes to complete.

4. Allow us to obtain information from their medical record.

   Once participants agree, researchers can review their medical records now and in the future to gather medical information needed for research. Looking at health records allows researchers to learn information that might be helpful during specific studies. Participants will not be informed if researchers look at their medical records.

Participants of the study, in the future, may also be asked to:

1. Complete additional questionnaires.

   We may occasionally send additional questionnaires to participants at home. They will take less than five minutes to complete. Participants can decide if they wish, to complete and return them. Biobank staff will not contact participants more than twice a year (and generally much less). Such contact does not mean that anything has been learned about the participants' health.

2. Provide an additional blood sample.

   We may ask participants for additional samples in order to study changes in blood over time, or because we used up the first sample provided. If we ask for another sample, participants may always say no.

Are there any risks of participation?

Risks of participating in the Mitochondrial Disease Biobank include having your blood draw. The risks of drawing blood include pain, bruising, or rarely, infection at the site of the needle stick. There is minimal risk to participants for taking part in this research.

How are samples and information stored?

None of the samples in the Mitochondrial Disease Biobank will be stored with names, addresses, clinic numbers, birth dates, or social security numbers on them. Instead, samples will be assigned a unique code. No one will know which sample is a particular participant's just by looking at the label. Only certain members of the Mitochondrial Disease Biobank staff and Biospecimen Trust Oversight Group (BTOG) will know how to determine what participant goes with what sample.

For example:

How will researchers access participants' information?

The Mitochondrial Disease Biobank will allow researchers access to the biobank samples only after a strict application and review process. We will then provide them with anonymized tissue sample(s) and some medical information (clinical symptoms, age, sex, diagnosis, etc) linked to that sample, but Mayo will not provide a name, address, phone number, social security number, or any other identifying information.

How is the Mayo Clinic Mitochondrial Disease Biobank funded?

The Mitochondrial Disease Biobank is funded by a generous private donation.