MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes)
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A teenager with short stature, diabetes, and sensorineural hearing loss has recurrent episodes resembling strokes that don't follow vascular territories. Lactate is elevated.
Maternal (mtDNA); MT-TL1 m.3243A>G (~80%)
- Stroke-like episodes (non-vascular distribution, often posterior)
- Lactic acidosis
- Myopathy
- Seizures
- Diabetes, deafness, short stature
- Ragged red fibers on muscle biopsy
- Elevated lactate (serum and CSF); lactate peak on MR spectroscopy of stroke-like lesions
- Molecular testing for the m.3243A>G MT-TL1 variant (urine sediment or buccal cells preferred over blood, where heteroplasmy may be low)
- Muscle biopsy: ragged red fibers, COX-positive fibers; respiratory chain enzyme analysis if molecular testing nondiagnostic
- Supportive: anticonvulsants for seizures (avoid valproate, which can worsen mitochondrial function)
- L-arginine (IV during acute stroke-like episodes, oral for prophylaxis) is used in some protocols
- Surveillance for diabetes, cardiomyopathy, and hearing loss; avoid mitochondrial toxins (aminoglycosides, metformin)
- Genetic counseling for maternal inheritance with variable heteroplasmy
m.3243A>G in tRNA-Leu: 80% of MELAS cases are caused by a single point mutation. The name itself is the mnemonic: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes.
Combined Complex I, III, and IV deficiency: because the mutation is in a mitochondrial tRNA (not a single complex subunit), multiple respiratory chain complexes are affected.