A Rare Heteroplasmic MT-ND5 Mutation (m.13094T>C) in an Iranian Patient with Adult-Onset MELAS: Diagnostic Challenges and Therapeutic Implications

Abstract

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [MELAS] is arare multisystem mitochondrial cytopathy that is highly heterogeneous in severity andclinical 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 inMT-ND5 are increasingly recognized but poorly characterized.This report documents the case of a 37-year-old Iranian woman diagnosed withMELAS. 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 tissue-specific effects. 3.Ethnic diversity in mtDNA mutations warrants broader geneticscreening in non-classical cases.