The clinical picture is highly variable. Most commonly patients have myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. The onset of symptoms is usually in the first two decades of life, most commonly consisting of headaches of sudden onset accompanied by vomiting and seizures. The headaches may simulate migraines. Weakness, lethargy, and apathy may be present early. However, infants and young children may present with failure to thrive, developmental delay, and learning disabilities. Neurosensory deafness is often seen and peripheral neuropathy is usually evident. MRIs may show cerebellar hypoplasia and infarctions in the cerebral hemispheres. Some patients have calcifications in the basal ganglia. Patients may develop lactic acidosis. Muscle biopsies often show ragged, red fibers. The heart is commonly involved with both structural and rhythm defects. Depending upon the degree and location of brain damage, patients may have hemiparesis, lethargy, ataxia, myoclonic jerks, cognitive decline, and dementia. Morbidity and mortality are high.
