Unveiling a Novel MT-TS1 m.7479G>A in Mitochondrial Diabetes: The Critical Role of mtDNA Sequencing in Atypical Cases

Mitochondrial diabetes is a rare form of diabetes mellitus caused by mitochondrial DNA (mtDNA) mutations, often presenting with atypical features and maternal inheritance. We report a 71-year-old white female presenting with diabetes diagnosed at age 50, managed with oral therapy, who exhibited significant weight loss and a strong maternal family history of diabetes. Glutamic acid decarboxylase and insulinoma-associated-2 antibodies were negative with normal C-peptide, and genetic testing revealed a heteroplasmic <i>MT-TS1</i> m.7479G>A variant (13.90%). Glycemic management was achieved with metformin and gliclazide, and at 21 years post diagnosis, the patient maintained stable glycemic control with a glycated hemoglobin A_1c of 6.5% (SI: 48 mmol/mol) (reference range, 4.0%-6.0% [SI 20-42 mmol/mol]) without insulin. The <i>MT-TS1</i> m.7479G>A variant is implicated as a pathogenic cause of mitochondrial diabetes, highlighting the importance of mtDNA sequencing in atypical cases with maternal inheritance, the potential for milder phenotypes with low-heteroplasmy variants, and the critical role of genetic counseling.