Tehran University of Medical Sciences Case Reports in Clinical Practice 2538-2683 10 2 2025 10 15 83 89 Hamed Amirifard Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Mojtaba Shahbazi Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Ghasem Farahmand Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Maryam Kaeedi Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Sanaz Heydari Havadaragh Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. 2025 07 30 2025 09 08 Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [MELAS] is a rare multisystem mitochondrial cytopathy that is highly heterogeneous in severity and clinical presentation, mostly caused by diverse mutations in the mitochondrial DNA. While m.3243A>G is the most common variant, rare mutations like m.13094T>C in MT-ND5 are increasingly recognized but poorly characterized. This report documents the case of a 37-year-old Iranian woman diagnosed with MELAS. Her clinical manifestations include recurrent episodes of stroke-like events, focal seizures, and elevated serum and CSF lactate. Mitochondrial DNA analysis [mtDNA] was positive for a very rare pathogenic point mutation [mtDNA; m.3243A>G] in the MT-ND5 gene, with a heteroplasmy level of 8.2%. This case highlights: 1. Adult-onset MELAS with MT-ND5 mutations is underdiagnosed. 2.Low heteroplasmy (8.2%) may still cause severe phenotypes, suggesting tissuespecific effects. 3.Ethnic diversity in mtDNA mutations warrants broader genetic screening in non-classical cases. https://crcp.tums.ac.ir/index.php/crcp/article/view/1083 https://crcp.tums.ac.ir/index.php/crcp/article/download/1083/723