Leigh syndrome, caused by dysfunction in mitochondrial energy metabolism, is an inherited, heterogeneous, and progressive neurodegenerative disorder of infancy and childhood. From 1983 to August 2006, 14 cases diagnosed with Leigh syndrome were studied in terms of characteristic neuroimaging findings and abnormal mitochondrial configurations under electron microscopy, as well as molecular analysis. Of the 14 cases, 11 presented clinical features before age 1 (79%). All 14 presented with variable symptoms of central nervous system involvement. The three most common symptoms were developmental delay (12/14; 86%), seizures (11/14; 79%), and altered consciousness (8/14; 57%). Extra-central nervous system manifestations were observed in 10 of the 14 cases, the most common symptoms being failure to thrive (5/14; 36%), pericardial effusion and dilated cardiomyopathy (3/14; 21%), and liver function impairment (3/14; 21%). In all 14 cases, neuroimaging revealed abnormal findings over the basal ganglion, brainstem, or both. The putamen was the most common lesion site in the basal ganglia (11/12; 92%). Cranial magnetic resonance imaging was used for follow-up in 6 cases because of changes in clinical features; in all 6 cases the imaging revealed evolution in the brain. Cranial magnetic resonance spectroscopy was performed in 3 cases and in 2 of them revealed lactate peaks during deterioration of the disease course. The prognosis for Leigh syndrome was poor during long-term follow-up. Seven cases were early fatalities, before 1 year and 6 months of age. Follow-up cranial magnetic resonance imaging together with magnetic resonance spectroscopy in cases with clinical evolution is helpful for monitoring this disease.