The Natural History of Mitochondrial Diseases

Primary Mitochondrial Disease (MITO) is a serious and debilitating condition, often multi-systemic and requiring life-long monitoring and treatment of symptoms to reduce the risk of life-threatening episodes, metabolic crises, or acute illness. Although rare, MITO is the most common group of inherited metabolic diseases and is associated with abnormalities of the mitochondrial respiratory chain, which carries out oxidative phosphorylation to produce ATP (Gorman et al. 2016).

In adults, MITO is often a progressive multisystem disorder, with frequent, long-term monitoring and symptom management required to reduce the risk of an acute illness, and/or other life-threatening episodes and metabolic crises

Given that mtDNA mutations are typically transmitted through the maternal line, paternally related family members are not at risk and will represent asymptomatic controls. In sporadic cases such as chronic progressive external ophthalmoplegia (CPEO) that are typically caused by sporadic mtDNA deletions, family members are not at risk of carrying the disorder, and thus can act as family member controls. Similarly, those family members of participants with a nuclear DNA mutation such as autosomal dominant mitochondrial disease (e.g., OPA1 gene), and who do not carry the affected gene are also suitable asymptomatic controls.

This study will establish the AMDC Clinical Registry at NeuRA. Patients with confirmed MITO (the presence of pathogenic nuclear or mitochondrial DNA variants/deletion) and control participants that can include: biological relatives of MITO participants with no clinical disease and no genetic risk; participants with a clinically confirmed non-MITO neurologic disorder or age and gender-matched healthy controls followed over at least 120 months (10) years.

Study data will include detailed medical and social history, summary of clinical presentation and clinical social history collected through diaries or on clinical review; neurological examination findings; results of investigations performed as standard of care, including laboratory findings through blood tests, imaging studies, cardiac investigations, gastrointestinal transit studies, neurophysiological studies, and analysis of archived muscle and/or skin biopsies.