Objective: To present a novel mitochondrial DNA mutation in a diabetic family
Research design and methods: The proband was a 64-year-old man. In the family, diabetes was maternally inherited. He had diabetes, cerebellar ataxia, cervical lipoma, hearing loss, olfactory dysfunction, ophthalmoplegia, and facial nerve bilateral palsy. On examination, early insulin secretion was blunted, and the M value on glucose clamp test was low. In muscle, ragged red fibers were not found. T-to-C mutation at position 3264 was detected in the proband (0.5% mutant DNAs in leukocyte and 30% in muscle), but was not detected in 201 normal individuals.
Results: Heteroplasmy of mutation, maternal inheritance of diabetes, and symptoms related to mitochondrial dysfunction suggest the pathogenecity of this 3264 mutation. As for diabetes etiology, both impaired insulin secretion and decreased insulin sensitivity seem to be important. In phenotypic characteristics, the combination of cerebellar ataxia and lipoma is a symptom sometimes found in myoclonic epilepsy and ragged red fibers (MERRFs). Ophthamoplegia is a symptom of chronic progressive external ophthalmoplegia (CPEO). These suggest that our proband had phenotypic overlap with MERRF and CPEO. Conversely, facial nerve bilateral palsy is a rare finding. The pictures that focused on his cranial nerves were thus unique, suggesting the heterogeneity of mitochondrial DNA (mtDNA)-related diabetes.
Conclusions: A novel 3264 mitochondrial DNA mutation in diabetes gives new insight to the etiology of mitochondrial diabetes. Its pathogenecity supports the belief that the tRNA(Leu)(UUR) gene is an etiological hot spot of mitochondrial diseases.