Mitochondrial disease

•Mitochondrial diseases are disorders of energy metabolism that include defects of pyruvate metabolism, Krebs cycle, respiratory chain (RC), and fatty acid oxidation (FAO).•Treatment of pyruvate metabolism, Krebs cycle, and RC disorders is, in general, disappointing. Therapeutic approaches consist of electron acceptors, enzyme activators, vitamins, coenzymes, free-radical scavengers, dietary measures, and supportive therapy. These treatment assumptions are based on current understanding of the pathophysiology, on anecdotal clinical reports, and on a few controlled clinical trials, which have not been encouraging. Although it is difficult to perform clinical trials in these conditions due to their rarity and genotypic and phenotypic heterogeneity, there is a great need for well-performed double-blind placebocontrolled clinical trials with comparable groups of patients and with sufficient follow-up periods.•Treatment options for FAO disorders are, in general, satisfactory and are mainly based on diet, lifestyle recommendations, and administration of L-carnitine and, in some cases, riboflavin.•Special conditions that involve primary deficiencies of L-carnitine, coenzyme Q10, and cofactor- and vitamin-responsive enzyme defects must be systematically considered, because supplementation with these substances may be curative or produce dramatic improvements.•While awaiting more specific therapies for mitochondrial disorders, it is useful to reach a consensus regarding the management of these patients. The expected outcome is a slowing of the disease process and stabilization of the clinical syndrome. More definitive treatments hopefully will follow in the near future.