DS promotes a significant metabolic reprogramming of RBCs. Levels of metabolites involved in glycolysis, glutathione homeostasis, carboxylic acids, and purine metabolism are significantly increased in RBCs from individuals with T21 (dark blue) when compared with age-matched disomic individuals (red) (y-axis = arbitrary units). **P < .01; ***P < .001; ****P < .0001, Student t test.