A New Mitochondrial tRNA(Met)—Gene Mutation in a 12-Year-Old Boy with MELAS: Clinical Presentation and Effects of Arginine Treatment

Introduction: MELAS syndrome is a mitochondrial (mt) DNA disorder with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes as main features. Fourteen different point mutations in six different mitochondrial tRNA genes have been identified so far. The clinical course is progressive leading to mental deterioration and neurological deficits. We report on the first identification of a heteroplasmic point mutation in the mitochondrial tRNA gene for Methionine.

Case Report: Neuronal deafness was diagnosed at age 9 years in a so far healthy boy now 12 years of age. In his 10 years of life, he suffered from tonic-clonic seizures, which stopped under Levetiracetam. At the age of 11.5 years, a severe attack of headage with flittering occurred suddenly. Cranial MRI revealed ischemic alterations in the territory of Aa. cerebri posterior and media right, which recede completely within weeks. Diagnostic workup showed elevated CSF lactate and plasma “Fibroblast Growth Factor (FGF)—21” levels. In muscle biopsy, “Ragged Red Fibers” and cytochrome c-oxidase—negative fibers in mosaic could be seen. Sanger sequencing of all mt tRNA genes identified a so far unknown heteroplasmatic point mutation in the tRNA(Met) gene: T4414C. The clinical course was characterized by repeated episodes with seizures, headage and flittering, which diminish rapidly by parenteral Arginine administration and did not show any correlates on MRI.

Conclusion: The mtDNA mutation described here is the first one which could be identified in the mitochondrial tRNA gene for Methionine in a subject with MELAS and is expected to alter biosynthesis of all mitochondrial DNA encoded subunits of the respiratory chain.