Mitochondrial Myopathy Rating Scale

The goal of this observational study is to develop and validate tools to measure disease course in patients with primary mitochondrial myopathy (PMM). The main aims of this study are:

* Development, validation, and optimization of objective outcome measures for mitochondrial myopathy
* Defining the natural history of mitochondrial myopathy

Researchers will compare data from patients with primary mitochondrial myopathy to healthy controls. Data from healthy controls will also help define normative data for future studies.

Participants will perform clinical exams of muscle strength and endurance and will complete surveys.

Currently, natural history knowledge is limited for all PMM. The clinical phenotype and disease course may be distinct depending on the PMM genetic etiology, however variability between family members harboring the same genetic mutation is also well described.

A major barrier to precise documentation of clinical progression has been the absence of meaningful and validated PMM-specific outcome measures. The long-term goal of these cumulative studies is to promote robust PMM clinical trial design and drug approval, as facilitated by natural history data and validation of PMM-specific objective outcome measures that enable accurate quantitation of symptoms. The overarching hypothesis is that deeper understanding of mitochondrial myopathy will promote meaningful clinical trial design. This study is approved under Children's Hospital of Philadelphia (CHOP), Institutional Review Board (IRB) protocol (#16-013364, PI Zolkipli) and is supported by a research infrastructure that includes physical therapists, biostatistician and bioinformatician for automated clinical data extraction from medical records.

Eligibility Criteria:
MM Cohort Inclusion Criteria

1. Males or females age 0-100 years of age
2. Mitochondrial disorder established by confirmed genetic or biochemical mutation in mtDNA or nuclear DNA OR is suitable for participation in the opinion of the investigator based on clinical presentation.
3. Exhibits myopathy (exercise intolerance, muscle strength, fatigue) relating to Mitochondrial disease in the opinion of the investigator
4. Able to provide written consent OR parental permission and child assent OR if they are an adult with diminished capacity, an LAR or healthcare representative is able to and willing to provide consent ., as approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)

MM Cohort Exclusion Criteria

1. Male or female fetuses
2. Non English speakers
3. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
4. Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations of these criteria must be reported in accordance with IRB Policies and Procedures.

Healthy Control Cohort Inclusion Criteria

1. Males or females age 0-100 years of age
2. No history of mitochondrial myopathy symptoms
3. Able to provide written consent or parental permission and child assent., approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)
4. Individual is not a study staff member or a family member of a study staff member (not listed as a study staff in eIRB)

Healthy Control Exclusion Criteria

1. Male or female fetuses
2. Non English speakers
3. Mitochondrial disorder established by confirmed genetic or biochemical mutation in mtDNA or nuclear DNA
4. Exhibits myopathy (exercise intolerance, muscle strength, fatigue) relating to Mitochondrial disease
5. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
6. Individual is listed as a study staff member in eIRB, OR individual is a family member of a study staff member listed in eIRB
7. Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations of these criteria must be reported in accordance with IRB Policies and Procedures.