Background: Mitochondrial disorders (MD) are multisystem diseases that arise as a result of dysfunction of the oxidative phosphorylation system. The predominance of neuromuscular manifestations in MD could mask the presence of other clinical phenotypes such as cardiac dysfunction. Reported here is a retrospective study, the main objective of which was to characterize the clinical and molecular features of a cohort of patients with cardiomyopathy and MD.
Methods and results: Hospital charts of 2,520 patients, evaluated for presumed MD were reviewed. The clinical criterion for inclusion in this study was the presence of a cardiac disturbance accompanied by a mitochondrial dysfunction. Only 71 patients met this criterion. The mitochondrial genome (mtDNA) could be sequenced only in 45 and the pathogenicity of 2 of the found changes was investigated using transmitochondrial cybrids. Three nucleotide changes in mtDNA that may be relevant and 3 with confirmed pathogenicity were identified but no mutations were found in the 13 nuclear genes analyzed.
Conclusions: The mtDNA should be sequenced in patients with cardiac dysfunction accompanied by symptoms suggestive of MD; databases should be carefully and periodically screened to discard mitochondrial variants that could be associated with MD; functional assays are necessary to classify mitochondrial variants as pathogenic or polymorphic; and additional efforts must be made in order to identify nuclear genes that can explain some as yet uncharacterized molecular features of mitochondrial cardiomyopathy.