Short telomeres in mitochondrial DNA depletion disorders

• In a cohort of patients with mitochondrial DNA depletion disorders, telomere length was significantly shorter than healthy controls. • The difference in telomere length was most pronounced in granulocytes. • Telomere length may have potential as a biomarker in mitochondrial disease. Mitochondrial DNA (mtDNA) depletion disorders (MDDs) are rare, genetically diverse conditions marked by a significant reduction in mtDNA, primarily affecting energy-demanding tissues such as muscle, liver, and brain, sometimes leading to catastrophic multisystem failure. In a cohort of patients with MDDs, we measured telomere length in lymphocytes, granulocytes, T cells, and B cells, and compared to healthy controls. Telomere length was shorter overall in patients with MDDs, with the most significant differences observed in granulocytes. The observation that mtDNA depletion is associated with shorter telomeres may provide insight into MDD pathophysiology. Telomere length may have potential as a biomarker in mitochondrial disease, but further study is needed.