Acute Infection in Mitochondrial Disease: Metabolism, Infection and Immunity

Study Description: A prospective longitudinal natural history study of acute illness in participants with Mitochondrial Disease and household/family members. Objectives: Primary Objectives: To identify immune signatures that associate with host responses to disease that would allow improved patient stratification and identification of potential therapeutic targets to mitigate the severe symptoms and sequelae of infection in mitochondrial disease. Secondary Objectives: 1. To correlate immune signatures with quantifiable measures of clinical presentation to biomarkers of vulnerability and recovery and understand how these measures evolve over time. 2. To perform exploratory analyses of omic variants, epigenetic signatures, serologic immune markers, antibody profiles and other possible techniques to discover other mechanisms of disease and their relationship with patient-centered outcomes. Endpoints: Primary Endpoints: We will perform whole blood transcriptomic analysis, humoral response profiling and soluble mediator profiling. Secondary Endpoints: 1. We will collect patient medical records for data abstraction to stratify severity of illness based on clinical factors (e.g. intensive care status, ventilatory support, clinical laboratory data, radiology records), 2. We will collect patient centered outcomes data via questionnaires to understand functional status, healthcare resource access and other sociodynamic factors as they affect the mitochondrial disease community. Exploratory Endpoints: 3. We will collect whole blood specimens for sera and DNA that will support these activities, which will be developed dynamically during the protocol. This will include next generation sequencing to identify biomarkers associated with parameters of infection and recovery. 4. We will collect other biological specimens (e.g. cerebral spinal fluid) where possible for the exploratory analyses outlined above.