Heme A is the prosthetic group of cytochrome c oxidase, the terminal enzyme in the respiratory chain. It is formed by the action of cytochrome c oxidase assembly protein COX15 homolog (COX15) on heme O (Petruzzella et al. 1998, Antonicka et al. 2003). Defects in COX15 cause of mitochondrial complex IV deficiency (MT-C4D; MIM:220110), also called cytochrome c oxidase deficiency resulting in a disorder of the mitochondrial respiratory chain seen as heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs (Antonicka et al. 2003). Defects in COX15 also cause Leigh syndrome (LS; MIM:256000), an early-onset progressive neurodegenerative disorder characterised by the presence of focal, bilateral lesions in one or more areas of the central nervous system (Oquendo et al. 2004, Bugiani et al. 2005).