MELAS syndrome with m.3243A>G heteroplasmic variant in a 12‑year‑old girl complicated by mitochondrial‑related diabetes: a case report

Background: Mitochondrial encephalomyopathy, lactic acidosis, and stroke‑like episodes (MELAS) is a heteroplasmic mitochondrial disorder most frequently caused by the m.3243A>G pathogenic variant in the MT‑TL1 gene¹. Although neurological manifestations are well documented in paediatric populations, multisystem involvement including acute mitochondrial diabetes is an atypical early presentation that frequently leads to diagnostic delay and misdiagnosis ^6,8 . Case presentation: A previously healthy 12‑year‑old girl presented with intermittent seizures for one month and acute fever accompanied by severe headache for one day. Serial cranial MRI demonstrated dynamically evolving, non‑vascular territorial stroke‑like lesions located in the right temporo‑parieto‑occipital lobe and thalamus. Laboratory examination revealed mildly elevated blood lactate. During hospitalization, the patient developed unexpected severe hyperglycaemia combined with metabolic acidosis, indicating multisystem mitochondrial dysfunction. Family genetic testing confirmed a heteroplasmic m.3243A>G variant with a heteroplasmy rate of 66.43%. Seizures were controlled with levetiracetam, and standardized mitochondrial supportive cocktail therapy was administered. Acute mitochondrial diabetes was corrected with insulin therapy. One‑month follow‑up showed complete clinical remission, remarkable resolution of intracranial lesions, and stable glycaemic control. Conclusion: MELAS syndrome should be highly suspected in paediatric patients presenting with recurrent seizures, migratory stroke‑like brain lesions, and unexplained new‑onset diabetes, particularly in the context of maternal metabolic disease history. Combined metabolic screening, serial neuroimaging, and mitochondrial genetic testing enable early and accurate diagnosis. Multidisciplinary individualized management improves long‑term clinical outcomes ⁷.