• Fernando Scaglia and Jennifer L Northrop.
• Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA. fscaglia@bcm.tmc.edu
• Cns Drugs. 2006 Jan 1; 20 (6): 443-64.

AbstractMitochondrial encephalomyopathies are a multisystemic group of disorders that are characterised by a wide range of biochemical and genetic mitochondrial defects and variable modes of inheritance. Among this group of disorders, the mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome is one of the most frequently occurring, maternally inherited mitochondrial disorders. As the name implies, stroke-like episodes are the defining feature of the MELAS syndrome, often occurring before the age of 15 years. The clinical course of this disorder is highly variable, ranging from asymptomatic, with normal early development, to progressive muscle weakness, lactic acidosis, cognitive dysfunction, seizures, stroke-like episodes, encephalopathy and premature death. This syndrome is associated with a number of point mutations in the mitochondrial DNA, with over 80% of the mutations occurring in the dihydrouridine loop of the mitochondrial transfer RNA(Leu(UUR)) [tRNA(Leu)((UUR))] gene. The pathophysiology of the disease is not completely understood; however, several different mechanisms are proposed to contribute to this disease. These include decreased aminoacylation of mitochondrial tRNA, resulting in decreased mitochondrial protein synthesis; changes in calcium homeostasis; and alterations in nitric oxide metabolism. Currently, no consensus criteria exist for treating the MELAS syndrome or mitochondrial dysfunction in other diseases. Many of the therapeutic strategies used have been adopted as the result of isolated case reports or limited clinical studies that have included a heterogeneous population of patients with the MELAS syndrome, other defects in oxidative phosphorylation or lactic acidosis due to disorders of pyruvate metabolism. Current approaches to the treatment of the MELAS syndrome are based on the use of antioxidants, respiratory chain substrates and cofactors in the form of vitamins; however, no consistent benefits have been observed with these treatments.

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