Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome

Leigh disease is a subacute neurodegenerative disorder characterized by sym metric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain s tem, and optical nerves and caused by altered oxidative phosphorylation. We describe the clinical, biochemical, neuroimaging, and molecular studies of a 19-year-old boy with early-onset Leigh disease manifesting as severe ext rapyramidal disorder with generalized dystonia and choreoathetosis. He was born of healthy parents after an uneventful pregnancy and delivery. At the age of 2 1/2 years, after a minor respiratory infection, he developed unsta ble, broad-based gait and tremor of the hands. These symptoms persisted for the next several years, when ataxia became more prominent. Difficulty in s wallowing, dysarthria, trunk dystonia, and marked dyskinesia of the arms an d hands gradually developed. Nystagmus, transient ptosis, and strabismus al so appeared. Abnormal laboratory findings included elevated plasma and cere brospinal fluid lactate and pyruvate, with an abnormal lactate/pyruvate rat io. Cranial computed tomography and magnetic resonance imaging demonstrated signs of cerebellar atrophy, bilateral and symmetric hypodensities in the lentiform nucleus and thalamus, and transient hyperintensities of cerebral peduncles in T-2-weighted sequences suggestive of Leigh disease. Muscle bio psy revealed isolated fiber atrophy, necrotic fibers undergoing phagocytosi s, and no ragged-red fibers. The measured catalytic activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a partial cytochrome c oxidase deficiency. No abnormalities in the mitochondrial genome and in t he SURF-1 gene were found. The boy is currently receiving levodopa therapy, creatine monohydrate, and a high dosage of thiamine and lipoic acid, his c ondition is stabilized, and extrapyramidal symptoms are less pronounced.