Foundations · Year 1 · from Foundations
Case 2: MELAS Syndrome (Mitochondrial DNA Mutation)
Clinical Image
Source: Radiopaedia - MELAS syndrome - CC BY-NC-SA 3.0
Case Presentation
A 19-year-old woman presents with sudden onset of right-sided weakness and visual disturbance. She has a history of recurrent migraine-like headaches, hearing loss, and exercise intolerance since childhood. Her mother and maternal aunt both have diabetes and hearing loss. Physical examination reveals right hemiparesis and right homonymous hemianopia. Initial CT head is negative for hemorrhage. MRI shows cortical and subcortical T2 hyperintensities in the left parieto-occipital region that do not conform to a single vascular territory. Laboratory studies reveal elevated serum lactate (4.8 mmol/L) and elevated lactate in CSF. Given the stroke-like presentation in a young patient with maternal family history and multisystem involvement, MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is suspected. Genetic testing confirms the m.3243A>G mutation in the MT-TL1 gene encoding mitochondrial tRNA-leucine. She is treated supportively with L-arginine (a nitric oxide precursor that may improve cerebral blood flow) and coenzyme Q10 supplementation. The family is counseled about maternal inheritance.
Key Learning Points
- MELAS is caused by mutations in mitochondrial DNA, most commonly m.3243A>G in the tRNA-leucine gene, which impairs mitochondrial protein synthesis and electron transport chain function
- Mitochondrial diseases follow maternal inheritance because mitochondria are transmitted exclusively through the oocyte; variable heteroplasmy (proportion of mutant vs. normal mtDNA) explains the phenotypic variability
- Tissues with high energy demands (brain, muscle, heart, retina) are most affected; chronic lactic acidosis results from impaired oxidative phosphorylation shunting pyruvate to lactate