Primary Mitochondrial Disease (PMD) is a genetic neurometabolic disorder, leading to central nervous system degeneration and increased risk of early mortality. There is a strong link between the pathophysiology of mitochondrial disease and biomarkers related to the biochemistry of redox imbalance, involving the levels of glutathione. Investigators will use Magnetic Resonance Imaging and Spectroscopy to non-invasively measure glutathione and other chemicals in the brain to identify redox imbalance in patients with PMD.
Primary Mitochondrial Disease (PMD) is a genetic neurometabolic disorder, leading to the degeneration of the central nervous system (CNS) and increased risk of early mortality. PMD can be caused by mutations in several genes in the mitochondrial DNA as well as nuclear DNA. Although a rare disease, PMD can significantly impact quality of life, increasing healthcare costs and caregiver burden. There is a lack of non-invasive, validated, and objective markers of mitochondrial function. However, there is a strong link between the pathophysiology of mitochondrial disease and biomarkers related to the biochemistry of redox imbalance, involving the levels of glutathione (GSH). Redox imbalance can also result in the overgeneration of radicals, causing neuronal damage. With the advancement in magnetic resonance techniques, the investigators can measure the levels of GSH and other neurochemicals non-invasively in the brain. Investigators in this proposal will use Magnetic Resonance Spectroscopy and Imaging (MRS and MRI) to measure brain chemicals, structure, and function.
Study Type
OBSERVATIONAL
Enrollment
30
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
RECRUITINGAssess group differences in brain chemical levels in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Metabolite concentrations from H Magnetic Resonance Spectroscopy (MRS) will be processed in Osprey followed by linear combination modelling of MRS spectra. Water-scaled metabolite estimates will be calculated and corrected for tissue composition and relaxation effects to generate metabolite concentrations.
Time frame: Approximately 1 day
Change in Plasma glutathione levels in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Analyze and report plasma glutathione levels (µM) in affected cases versus healthy controls. Glutathione is an antioxidant that protects cells from oxidative stress and detoxification. Differences between the two groups is anticipated.
Time frame: Approximately 1 day
Change in Corticol Thickness in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Morphometric analyses and reporting of cortical thickness, surface area, and volume in affected cases versus healthy controls. Reporting cortical thickness involves using structural magnetic resonance imaging (MRI) to measure the width of the gray matter of the cortex, typically in millimeters, and analyzing regional variations to asses brain structure and function.
Time frame: Approximately 1 day
Change in Cerebral Blood Flow in Genetically Confirmed Primary Mitochondrial Disease (GC-PMD) compared to healthy controls (HC)
Cerebral blood flow imaging (using spin labeling or similar), analyses, and reporting in affected cases versus healthy controls. Studying blood flow in the brain can assess for cerebrovascular disease.
Time frame: Approximately 1 day
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