CARS2 and MERRF syndrome: Besides of these NFE2L3 (transcription factor) which involved in several cellular processes like inflammation, stress response, differentiation, and carcinogenesis (Kannan et al., 2015), MTHFD1 are key players in folate metabolism, which is essential for de novo purine synthesis, and several defects in this pathway have been associated with immunodeficiency (Keller et al., 2013), and CARS2 is associated with a severe progressive myoclonic epilepsy most resembling MERRF syndrome (Hallmann et al., 2014).