• myopathy
• mitochondrial disorders
• mitochondria
• neuromuscolar disorders

Mitochondrial disorders (MDs) are the most frequent metabolic deficits in human pathology, with a frequency of nuclear (nDNA) and mitochondrial DNA (mtDNA) pathogenic variants of 1: 4300. Myopathy may be the initial and isolated feature of MDs, or may occur in association with other manifestations, like deafness, polyneuropathy, ataxia, stroke-like episodes, diabetes, liver or kidney involvement. As recently proposed by an International consortium, “primary mitochondrial myopathies (PMM) are genetically defined disorders leading to defects of oxidative phosphorylation affecting predominantly, but not exclusively, skeletal muscle”.
Methods: Baseline data collection of 118 patients with PMM, followed by centres of the Italian network for mitochondrial diseases, using 6MWT, 3TUG, 5XSST, TWST, TOMASS as functional outcome measures, FSS and WHYMP as patients record outcome measures, FGF21, GDF 15, lactate ad CK as biomarkers.
Results: 118 PMM cases were included. Functional outcome measures (6MWT, 3TUG, 5XSST, TWST, TOMASS) and biomarkers significantly differed from healthy reference values and controls. Moreover, functional measures correlated with patients perceived fatigue and pain severity. Patients with either mitochondrial or nuclear DNA point mutations performed worse results in functional measures than patients harbouring single deletion, even if the latter had an earlier age at onset but similar disease duration. Biomarkers FGF21 and GDF15 were both significantly higher compared to a matched control population, whereas there was no relation with severity of disease.
Conclusions: We characterized a large cohort of PMM evaluating baseline mitochondrial biomarkers and functional scales that represent potential outcome measures to monitor the efficacy of treatment in clinical trials.