Dear Sirs, Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder causing selective loss of motor neurons in brain motor cortex and spinal cord in which muscle denervation and atrophy are associated with pyramidal involvement, typically spreading to contiguous muscular regions and leading eventually to a fatal paralysis. Here, we report two ALS cases carrying the m.11778A > G/ I MT-ND4 i (R340H) mitochondrial DNA (mtDNA) mutation pathogenic for Leber's hereditary optic neuropathy (LHON), a maternally inherited disease due to mtDNA mutations affecting complex I function and usually leading to isolated optic atrophy [[2]]. Pathogenic mtDNA mutations have been found in ALS phenocopies with a primary mitochondrial disorder [[12]] and, more recently, mutations in nuclear genes, such as I CHCHD10 i , have been associated with ALS and mitochondrial myopathy with accumulation of mtDNA multiple deletions [[13]]. [Extracted from the article]