Infantile presentation of the mtDNA A3243G tRNA(Leu(UUR)) mutation

Mitochondrial DNA (mtDNA) disorders are clinically very heterogeneous, rang ing from single organ involvement to severe multisystem disease. one of the most frequently observed mtDNA mutations is the A-to-G transition at posit ion 3243 of the tRNA(Leu) ((UUR)) gene. This mutation is often related to M ELAS syndrome. However, not all patients with the A3243G mutation share the same clinical disease expression and, on the contrary, patients clinically exhibiting MELAS syndrome may have other mtDNA mutations. Here we describe two patients with a very early infantile presentation of disease associate d with the A3243G mutation. Patient 1 presented with hypotonia, feeding dif ficulties and failure to thrive (FFT) at the age of 3 months. Laboratory in vestigations showed persistent hyperlactic acidemia, elevated lactate/pyruv ate ratios and elevated alanine concentrations in blood. Developmental dela y was progressive and he developed cardiomyopathy and seizures. Death occur red at the age of 3.5 years. Patient 2 was born prematurely and had persist ent, severe lactic acidosis from birth on. Moderate biventricular hypertrop hy was seen on ultrasound studies of the heart and, suffering from progress ive lactic acidosis, he died at the age of 13 days. Because of the rarity o f this very early presentation, we searched the literature for other infant ile cases associated with the A3243G mutation and found 8 additional ones. In infants presenting with lactic acidosis/ hyperlactic acidemia, failure t o thrive, hypotonia, seizures and/or cardiomyopathy, mtDNA mutational analy sis, also for the disease entities, usually only observed in juveniles or a dults is warranted.