199-LB: Mitochondrial Diabetes (MD) in the University of Chicago Monogenic Diabetes Registry

Abstract

Mitochondrial diabetes (MD) results from pathogenic variants in mitochondrial (MT) genes. MT disease is associated with neuromuscular disease. MD may occur either alone or with other conditions. The most common MD genetic variant is MT-TL1 m.3243 A>G, associated with Maternally Inherited Diabetes and Deafness and Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes. The incidence, variability and optimum treatment are uncertain. We describe clinical characteristics of participants in the Univ. of Chicago Monogenic Diabetes Registry with MD variants. Participants enrolled in the Univ. of Chicago Monogenic Diabetes Registry (IRB 6858,15617B). Clinical and genetic information was collected. As of February 2023, 18 participants from 13 families had a known MT variant. Clinical characteristics are in Table 1. Clinicians should consider MD when the patient is negative for T1D antibodies, is non-obese, has high frequency bilateral hearing loss, and has a strong maternal family history of diabetes. However, the features are variable and can include multiple organs and tissues. Genetic testing panels should include MT variants because MD can be misdiagnosed and the prevalence is uncertain. Clinical phenotypes are heterogenous among family members. Cascade testing and screening for related conditions is encouraged. Our data shows that MD is misdiagnosed as T1 or T2DM (16/16). Disclosure T. L. Bowden: Stock/Shareholder; Procter & Gamble, OPKO Biologics, Ltd. B. Kandasamy: None. L. R. Letourneau-freiberg: None. K. Rodriguez: None. M. Mccullough: None. S. W. Greeley: None. L. H. Philipson: Advisory Panel; Nevro Corp., Research Support; Novo Nordisk, Dompé, Provention Bio, Inc., Imcyse, Novo Nordisk Foundation. Funding National Institutes of Health (R01DK104942, P30DK020595, K23DK094866, UL1TR000430)