Markedly Different Clinical Features in 2 Diabetes Mellitus Patients with Extremely High Tissue Levels of the Mitochondrial DNA A3243G Mutation

Abstract

Background: Mitochondrial DNA (mtDNA) A3243G mutation is one of the major causative factors of mitochondrial diabetes mellitus. We found that tissues from 2 of 142 diabetes mellitus patients showed extremely high levels of the mutation. Objective: To investigate the level of the mutation in each tissue and to find the relationship between the mutation level and clinical features of the patients. Methods: Patient 1 was a 51-year-old woman, diagnosed as having diabetes mellitus at the age of 17, and was admitted to hospital because of cerebral infarction. Patient 2 was an 82-year-old woman who was admitted because of respiratory failure. mtDNA A3243G levels were measured in tissues collected at autopsy. Results: In patient 1, mtDNA A3243G levels were found to vary among the tissues. The patient’s highest mtDNA A3243G value was 42% and the lowest value was 9%, whereas the level in most individuals is usually less than 1%. Although patient 2 did not exhibit serious clinical symptoms of diabetes mellitus, the mtDNA A3243G level was extremely high in all of the tissues surveyed (range 32–47%). Conclusion: Although both patients showed high levels of the mtDNA A3243G mutation, their clinical conditions differed greatly. Thus, mitochondrial diabetes mellitus patients may show a wide variety of clinical features and large variations in life span.