A Subtype of Diabetes Mellitus Associated with a Mutation of Mitochondrial DNA

Abstract

Background: Several families have been described in which a mutation of mitochondrial DNA, the substitution of guanine for adenine (A--G) at position 3243 of leucine transfer RNA, is associated with diabetes mellitus and deafness. The prevalence, clinical features and pathophysiology of diabetes with this mutaion are largely undefined. Methods: We studied 55 patients with insulin-dpeendent diabetes mellitus (IDDM) and a family history of diabetes (group 1), 85 patients wiith IDDM andn no family history of diabetes (group 3), and 5 patients with diabetes and deafness (group 4) for the mutation. We also studied the prevalence and charactersitics of diabetes in 39 patients with a syndrome consisting of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes who were known to have the mutation and 127 of their relatives (group 5). Results: We identified 16 unrelated patients with diabetes associated with the A--G mutation: 3 patients from group 1 (6 percent), 2 patients from group 3 (2 percent), 3 patients from group 4 (60 percent), and 8 patients from group 5 (21 percent). We also identified 16 additional subjects who had diabetes and the mutation among 42 relatives of the patients with diabetes and the mutation in groups 1, 2, 3 and 4 and 20 affected subjects among the 127 relatives of the patients in group 5. Diabetes cosegregated with the mutation in a fashion consistent with maternal transmission, was frequently (in 61 percent of cases) associated with sensory hearing loss, and was generally accompanied by impaired insulin secretion. Conclusions: Diabetes mellitus associated with the A--G mutation at position 3243 of mitochondrial leucine transfer RNA represents a subtype of diabetes found in both patients with IDDM and patients with NIDDM in Japan.