Childhood onset mitochondrial myopathy and lactic acidosis caused by a stop mutation in the mitochondrial cytochrome c oxidase III gene

More than 100 mitochondrial (mt) DNA mutations have been described in association with different complex neurological disorders and with respiratory chain (RC) deficiency in the past decade. 1 Aside from more frequently reported mt tRNA mutations and deletions, a growing list of pathogenic mutations affecting structural genes of mtDNA encoded respiratory chain subunits, mainly cytochrome b and cytochrome c oxidase subunit genes, has now been reported in association with various mitochondrial disorders as well 2 and most of these mutations are thought to be of sporadic origin. [...]numerous mutations in nuclear genes involved in the assembly of COX (SURF1, SCO2, SCO1, COX10) have been described. 3 As with most mtDNA mutations, the clinical presentation of patients harbouring mutations in mt encoded COX subunit genes is highly variable, ranging from late childhood onset myopathy 4- 8 to severe childhood onset multisystem disorders, 9- 14 and this might be explained by the variable distribution and abundance of mutant mtDNA in different tissues and by different expression thresholds. 3 All mt COX subunit gene mutations reported to date are heteroplasmic and most of these mutations have a high rate of mutant DNA in skeletal muscle and a lower or undetectable level of the mutation in other tissues, except for one patient who presented with Leigh-like syndrome, myopathy, and systemic COX deficiency 10 and who carried a virtually homoplasmic frameshift mutation in COIII in all tissues investigated.