Of the 15 formally defined mtDNA depletion syndromes listed in The Online Mendelian Inheritance in Man database (OMIM) [4], most are caused by pathogenic variants in proteins that are required for mtDNA replication (POLG, C10orf2, MGME1, and TFAM) or those that are necessary to maintain mitochondrial deoxyribonucleoside triphosphates (dNTP) pools (TK2, DGUOK, RRM2B, TYMP, SUCLA2, SUCLG1, AGK, MPV17 and SLC25A) [14, 48]. The gene discussed is AGK; the disease is mitochondrial DNA depletion syndrome.