MTO1-related mitochondrial disease (Combined Oxidative Phosphorylation Deficiency type 10, COXPD10; OMIM #614702) is a rare autosomal recessive disorder caused by biallelic variants in the nuclear MTO1 gene, which encodes an enzyme that modifies mitochondrial transfer RNA so that mitochondria can synthesise their proteins correctly. It typically presents in infancy with lactic acidosis and hypertrophic cardiomyopathy and, in longer-surviving children, evolves into a multisystem disorder with intellectual disability, epilepsy and optic neuropathy, a pattern termed ONCE syndrome (Optic Neuropathy, Cardiomyopathy, Encephalopathy with lactic acidosis and combined OXPHOS deficiency). We report a 12-year-old girl, the third child of consanguineous parents, with global psychomotor delay and persistent mild hyperlactataemia from infancy. Brain imaging showed symmetric T2 hyperintensity in both dentate nuclei with a cerebral lactate peak on MR spectroscopy. Whole-exome sequencing identified a homozygous MTO1 missense variant (c.1402G>A; p.Ala468Thr), consistent with the molecular diagnosis of COXPD10, with both parents heterozygous carriers; an incidental heterozygous FBN1 variant (p.Arg609Cys) was classified as a variant of uncertain significance and judged unrelated. She developed myoclonic epilepsy at age 11, managed with lamotrigine, while echocardiography and ophthalmological examination remained normal at age 12. We review the molecular pathogenesis, genotype-phenotype correlations and treatment options for MTO1 deficiency, focusing on dichloroacetate as adjunctive therapy for lactic acidosis and cardiomyopathy, and place the case alongside the 2025 FDA approval of elamipretide for Barth syndrome and emerging gene-therapy approaches. Early genetic diagnosis and structured cardiac and ophthalmological surveillance are essential; prospective studies of dichloroacetate are needed.