Glutamine Supplement in MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes) Syndrome

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder. The most common mutation is in the mtDNA gene MT-TL1 encoding the mitochondrial tRNALeu (UUR). For understanding the development of seizures in patients with mitochondrial disease, a study has recently emphasized the deficiency of astrocytic glutamine synthetase, creating a disinhibited neuronal network for seizure generation. The investigators propose to evaluate nine patients with mitochondrial DNA mutation and MELAS. Patients will receive oral supplementation with 10-15 g/day of glutamine (adjusted for weight and plasma concentrations). The primary outcome measures several amino acids (including glutamine) and lactate concentration measured in cerebrospinal fluid and cerebral lactate measured by magnetic resonance spectroscopy.

Inclusion criteria

• The diagnosis of MELAS syndrome is based on medical history (lactic acidosis, stroke-like episodes, and encephalomyopathy).
• Subjects have to be clinically stable for more than six months after any stroke-like episodes.
• All subjects have to be genetically confirmed.

Exclusion criteria

• Subjects harboring a MELAS-related pathogenic mtDNA mutation, no fulfilling the complete diagnostic criteria for the MELAS phenotype.