Evolution until death of two members of a family with A3243G mutation and MELAS phenotype versus diabetes mellitus

Introduction. The A3243G gene tRNA(Leu(UUR)) mutation has different phenotypic expressions. The clinical outcome and survival of each phenotype are mostly unknown. We followed-up two of three family members, carriers of the A3243G mutation, until their death. Clinical case. The proband case had MELAS (mitochondrial myopathy, encephalopathy, lactacidosis, stroke) phenotype. Although he presented with a stroke-like episode, he developed recurrent generalized and partial epileptic seizures without associated stroke-like episodes over time as well as slowly progressive dementia. The cognitive performance greatly worsened after a complex partial epileptic status. He died from bronchopneumonia and septic shock eleven years after diagnosis. His sister remains asymptomatic. His mother was diagnosed of diabetes mellitus and deafness when she was 53. Seventeen years later she developed a single stroke-like episode. She died one year after from acute renal failure and cardiogenic shock following sympathectomy for ischemic angiopathy. In the MELAS case neither idebenone treatment nor valproate substitution by other anticonvulsants reduced seizure frequency nor the spreading of lesions evaluated by MRI. In the phenotype with diabetes and deafness the outcome diabetes mellitus was as expected. Conclusions. In this family with A3243G mutation, the phenotype with neurosensorial deafness and diabetes mellitus seems to have longer survival than the MELAS phenotype. The cause of death in both cases was closely related to medical complications prevalent in each patient at the time of death.