Abstract
Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this disorder and showed recurrent metabolic abnormalities associated with this disease but not due to the diminished half-life of their erythrocytes. Glycolysis is exhausted with accumulation of ADP, pyruvate, lactate, and malate. Ascorbate metabolic pathway is altered probably due to a limited entry of dehydroascorbate. Although no major oxydative stress has been reported in patients with overhydrated hereditary stomatocytosis, we found decreased amounts of oxydized glutathione, creatine and ergothioneine, suggesting transporter abnormalities and/or uncharacterized oxydative stress. These results pinpoint major metabolic defects of overhydrated hereditary stomatocytosis erythrocytes and emphasize the relevance of red blood cell metabolomics for a better understanding of the pathophysiological bases of hemolytic anemia associated with erythrocyte abnormalities.