MELAS

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a progressive multisystem mitochondrial disorder that primarily affects the nervous system and muscles. It is one of the most common maternally inherited mitochondrial diseases, most frequently caused by the m.3243A>G mutation in the MT-TL1 gene encoding mitochondrial tRNA-Leu(UUR), though other mitochondrial DNA mutations have also been identified. The disease typically manifests in childhood or young adulthood, often after a period of normal early development. The hallmark features of MELAS include recurrent stroke-like episodes that cause temporary paralysis, vision abnormalities, and severe headaches, often accompanied by seizures. These stroke-like episodes predominantly affect the posterior regions of the brain and do not follow typical vascular territories. Patients characteristically have elevated lactic acid levels in the blood and cerebrospinal fluid, reflecting impaired mitochondrial energy production. Myopathy with exercise intolerance and muscle weakness is common. Additional features may include sensorineural hearing loss, diabetes mellitus, short stature, cardiomyopathy, cognitive decline, and gastrointestinal dysfunction. The disease is progressive, and repeated stroke-like episodes can lead to cumulative neurological damage. There is currently no cure for MELAS. Treatment is largely supportive and symptomatic. L-arginine has been used during acute stroke-like episodes and as a prophylactic measure, with some evidence suggesting it may reduce the severity and frequency of these episodes by improving nitric oxide-mediated vasodilation. Coenzyme Q10, B vitamins, and other mitochondrial supplements are commonly prescribed, though robust evidence for their efficacy remains limited. Seizure management requires careful selection of antiepileptic drugs, as valproic acid is generally contraindicated due to its potential to worsen mitochondrial dysfunction. Management of diabetes, cardiac complications, and hearing loss follows standard clinical guidelines. A multidisciplinary approach involving neurology, cardiology, endocrinology, and other specialties is essential for optimal care.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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