Leigh disease is a subacute
neurodegenerative disorder characterized by symmetric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, 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
extrapyramidal 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 unstable, broad-based gait and
tremor of the hands. These symptoms persisted for the next several years, when
ataxia became more prominent. Difficulty in swallowing,
dysarthria, trunk
dystonia, and marked
dyskinesia of the arms and hands gradually developed. Nystagmus, transient ptosis, and
strabismus also appeared. Abnormal laboratory findings included elevated plasma and cerebrospinal fluid
lactate and
pyruvate, with an abnormal
lactate/
pyruvate ratio. 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 T2-weighted sequences suggestive of
Leigh disease. Muscle biopsy revealed isolated fiber
atrophy, necrotic fibers undergoing phagocytosis, 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 the SURF-1 gene were found. The boy is currently receiving
levodopa therapy,
creatine monohydrate, and a high dosage of
thiamine and
lipoic acid, his condition is stabilized, and extrapyramidal symptoms are less pronounced.