Natural History Study - Mitochondrial Disease

Study Overview
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Brief Summary
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Carriers of the m.3242A>G mutation often have clinical symptoms which can include migraines, seizures, strokes, hearing loss, balance issues, gastrointestinal issues, and many other symptoms. The investigators would like to learn more about these disorders and have designed a Natural History Study to monitor these conditions over time so that physicians and scientists can not only understand the problems that patients have, but work on developing treatments. The focus of the current work is to evaluate known mutation carriers of the m.3243A>G (mitochondrial DNA) and their maternal relatives (carrier status not a requirement for participation). Paternal relatives will serve as controls. This study involves no treatment.

Detailed Description
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The purpose of this study is to investigate the neurological and biochemical consequences of the m.3243 A>G mutation. Mitochondria are the powerhouses of the cell and are controlled by nuclear genetic material (DNA) and mitochondrial (mt) DNA. Mitochondrial DNA mutations impair mitochondrial function, and cause cellular energy failure. These mutations, when present in high abundance, cause neurological signs and symptoms that are clinically obvious. The investigators hypothesize that these mutations, when present in lesser abundance, will cause measurable alterations in the patient's neuropsychological profile and cerebral energy profile. This study does not involve any experimental or approved therapy. The investigators will evaluate the patient's condition with blood/urine tests, neurological exam, MRI/MRS, questionnaires, motor skills functioning, serum and urine biomarkers, and genetic testing.

Official Title
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Mitochondrial Encephalomyopathies and Mental Retardation: Investigations of Clinical Syndromes Associated With MtDNA Point Mutations

Conditions
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MELAS or m.3243 A>G Mitochondrial DNA Mutation Carrier

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Known carrier of a the m.3243 A>G mitochondrial mutation, ,or Maternally related to someone who carries the m.3243A>G mitochondrial mutation. A family member who is not maternally related to someone who carries the m.3243A>G mitochondrial mutation Exclusion Criteria: Younger than 4 years of age No confirmed m.3243 A>G mitochondrial DNA mutation in the family.

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| mtDNA mutation<br>m.3243 A>G carriers and their maternal relatives Other mutations in the mitochondrial genome may be included | |
| Control<br>controls (people not maternally related to mutation carriers) Preference is for married in relatives | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI/MRS | Evaluate structure and function in brain and muscle | 2-3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers | Evaluate various biomarkers of disease progression | 2-3 years | 
| Motor skills | 6 minute walk test to evaluate motor skills | 2-3 years | 
| Cognitive function | Evaluate cognitive function through neuropsychological testing | 2-3 years | 
| Clinical symptoms | Evaluate clinical symptoms through medical history questionnaires and physical exam | 2-3 years | 
| Mutation load | Evaluate heteroplasmy through blood,urine and skin fibroblast evaluations | 2-3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MELAS, mitochondrial DNA mutation, mtDNA mutation, mitochondrial DNA, mitochondria, m.3243A>G mutation