Abstracts

Rationale: Epilepsy is a common feature of mitochondrial encephalopathies caused by defective oxidative phosphorylation in the central nervous system, typically associated with a number of other symptoms. Here we present a family with maternally inherited severe intractable epilepsy as the main symptom of mitochondrial disease due to a point mutation at position 616 in the mitochondrial tRNA-Phe (MT-TF) gene. Methods: Histological stainings were performed on skeletal muscle slices from the index patient. Oxidative phosphorylation activity was measured by oxygraphic and spectrophotometric methods. The patient's complete mitochondrial DNA (mtDNA) and the relevant mtDNA region in maternal relatives were sequenced. Mutation loads were determined by restriction-fragment length polymorphism. Results: Mosaic pattern of mitochondrial proliferation and cytochrome c oxidase (COX) deficiency, typical for pathogenic heteroplasmic mtDNA mutations, was not present in the skeletal muscle of the patient. Muscle histology showed only decreased overall COX staining. Biochemical analysis confirmed a combined respiratory chain defect, most severely affecting complex IV. Sequencing of the mtDNA revealed a mutation at position 616 in the gene for the mitochondrial phenylalanyl-tRNA (T>C). The mutation disrupts a Watson-Crick base pair in the anticodon stem at a highly conserved position. It was apparently homoplasmic in the patients, and had different heteroplasmy levels in healthy maternal relatives. Conclusions: Deleterious mutations in the mitochondrial tRNA-Phe may solely manifest with epilepsy when segregating to homoplasmy. They may be overlooked in the absence of lactate accumulation and typical mosaic mitochondrial defect in muscle.