Mitochondrial encephalomyopathy, lactic acidosis and cerebrovascular accidents (MELAS) in children with the A3243G mutation of the tRNA(Leu)(UUR) gene of DNA mitochondria

Objectives. To evaluate three patients with the mitochondrial encephalopathy, tactic acidosis and cerebrovascular accident syndrome (MELAS) diagnosed in childhood, with particular reference to the initial symptoms and clinical evolution during the first stage at a paediatric age, and to compare them with other studies on the subject. Patients and methods. Two boys and a girl of 10, 11 and 13 years had tests on lactate, pyruvate and aminoacids in biological fluids under basal conditions and also functional tests and enzyme activity assay of the mitochondrial respiratory chain of a muscle biopsy. We also analysed the particular DNA mutations related to MELAS in different tissues from these patients and in lymphocytes from members of the mothers' families who could be tested Results. The patients fulfilled the clinical criteria for the MELAS syndrome. Neuroimaging showed cerebrovascular accidents. Neurophysiological studies showed myopathy in one patient and neuroaxonal neuropathy in another In two cases ophthalmological study showed retinitis pigmentaria and during cerebrovascular accidents transient phenomena of homonymous hemianopsia and cortical blindness were seen. In all patients muscle biopsy showed ragged red fibres and the biochemical study show ed an enzyme deficit in the respiratory mitochondrial chain. On molecular genetic study of the mitochondrial DNA (mtDNA) there was a particular mutation A3243G on the tRNA((Leu)) in all patients and some members of the mothers:families. Conclusions. In children with frequent episodes of migraine headaches, vomiting, refractory epilepsy and fatigue the presence of a mitochondrial disease should be suspected. On detection of mtDNA mutations MELAS may be diagnosed even without all the clinical criteria which characterise this syndrome.