A SUBTYPE OF DIABETES-MELLITUS ASSOCIATED WITH A MUTATION OF MITOCHONDRIAL-DNA

Background. Several families have been described in which a mutation o f 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 pathoph ysiology of diabetes with this mutation are largely undefined. Methods . We studied 55 patients with insulin-dependent diabetes mellitus (IDD M) and a family history of diabetes (group 1), 85 patients with IDDM a nd no family history of diabetes (group 2), 100 patients with non-insu lin-dependent diabetes mellitus (NIDDM) and a family history of diabet es (group 3), and 5 patients with diabetes and deafness (group 4) for the mutation. We also studied the prevalence and characteristics of di abetes in 39 patients with a syndrome consisting of mitochondrial myop athy, encephalopathy, lactic acidosis, and stroke-like episodes who we re known to have the mutation and 127 of their relatives (group 5). Re sults. We identified 16 unrelated patients with diabetes associated wi th the A --> G mutation: 3 patients from group 1 (6 percent), 2 patien ts from group 3 (2 percent), 3 patients from group 4 (60 percent), and 8 patients from group 5 (21 percent). We also identified 16 additiona l 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 wit h maternal transmission, was frequently (in 61 percent of cases) assoc iated with sensory hearing loss, and was generally accompanied by impa ired insulin secretion. Conclusions. Diabetes mellitus associated with the A --> G mutation at position 3243 of mitochondrial leucine transf er RNA represents a subtype of diabetes found in both patients with ID DM and patients with NIDDM in Japan.