Melas

MELAS stands for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. It is a rare mitochondrial disorder caused by mutations in mitochondrial DNA, most commonly a point mutation at position 3243 (m.3243A>G) in the MT-TL1 gene encoding transfer RNA for leucine. The condition is inherited maternally and exhibits heteroplasmy, meaning both mutated and normal mitochondrial DNA are present in cells, leading to variable disease severity between individuals and even among organs within the same person.

Clinical features typically begin in childhood or early adulthood and can include recurrent stroke-like episodes with focal neurologic deficits, seizures, headaches, and cognitive impairment; chronic weakness and exercise intolerance; lactic acidosis; sensorineural hearing loss; diabetes and short stature may occur. The episodes resemble strokes but do not follow typical vascular territories, reflecting mitochondrial dysfunction rather than vascular occlusion.

Diagnosis involves clinical suspicion, neuroimaging showing non-vascular stroke-like lesions, elevated lactate levels, and genetic testing confirming pathogenic mtDNA mutations. Muscle biopsy may show ragged-red fibers, and other organ involvement may be assessed to guide management.

Management is supportive and multidisciplinary. There is no cure. Treatments focus on managing symptoms and preventing complications, including anticonvulsants for seizures, physical and occupational therapy, and metabolic supplements such as coenzyme Q10 or B vitamins in some cases. Some studies suggest L-arginine during acute stroke-like episodes; evidence remains limited. Patients are advised to avoid mitochondrial toxins, maintain good metabolic control, and receive genetic counseling due to maternal inheritance.

Prognosis varies widely; disease progression is common but the rate differs. MELAS is among the more frequently diagnosed mitochondrial disorders but remains rare overall.