Motor neuron disease in a patient with a mitochondrial tRNAIle mutation

Objective Motor neuron disease (MND) is a common neurodegenerative condition for which the underlying cause is uncertain in many patients. We identified a patient with clinical features suggestive of MND but additional cardiac and metabolic symptoms. We wished to determine if the clinical features were due to a mitochondrial DNA mutation. Methods The brain and spinal cord were studied using neuropathological techniques and agenetic defect investigated in individual neurons. Results There were atypical neuropathological features and genetic studies identified a pathogenic, heteroplasmic mitochondria tRNAIle (4274T>C) mutation. Interpretation This case adds to the phenotypic variation seen in mitochondrial DNA disease but also highlights the potential role of mitochondrial dysfunction in the cause of MND. Ann Neurol 2006