MITOCHONDRIAL ENCEPHALOPATHY, LACTIC-ACIDOSIS, AND STROKE-LIKE EPISODES (MELAS)

We report the clinical, pathological, and genetic findings of a case o f MELAS syndrome. This was a man who died for metabolic failure at the age of 27 years. His familiar history was positive for hypoacusia and stroke. He was of short stature and presented mild mental retardation . Since the age of 21 he suffered from recurrent brain-ischemic lesion s mainly in the occipital lobes, documented by repeated CT scans. The laboratory data and muscle biopsy disclosed lactic acidosis with ragge d red fibres. Neurophysiological data and peripheral nerve biopsy show ed an axonal neuropathy. A point mutation in the tRNA(Leu(UUR)) gene o f mitochondrial DNA was detected in 5 post-mortem tissues and in muscl e biopsy. No defects of mitochondrial respiratory chain were detected. The histological and ultrastructural studies of the brain showed mult iple and heterogeneous ischemic lesions with no obvious alterations of cerebral blood vessels. These lesions do not correspond to the vascul ar territories of main cerebral arteries. Our observations support the hypothesis that local metabolic alterations would play a crucial role in the pathogenesis of cerebral ischemic lesions in MELAS. The correl ation between genetic, biochemical, and pathological data are discusse d.