title: Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.
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.
authors.affiliation: Institut de Radiobiologie Cellulaire et Moléculaire, Laboratoire de Recherche sur la Réparation et la Transcription dans les Cellules, Gif-sur-Yvette cedex, France.
authors.forename: Dhouha
authors.initials: D
authors.lastname: Darghouth
authors.forename: Bérengère
authors.initials: B
authors.lastname: Koehl
authors.forename: Jean François
authors.initials: JF
authors.lastname: Heilier
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Madalinski
authors.forename: Petra
authors.initials: P
authors.lastname: Bovee
authors.forename: Giel
authors.initials: G
authors.lastname: Bosman
authors.forename: Jean
authors.initials: J
authors.lastname: Delaunay
authors.forename: Christophe
authors.initials: C
authors.lastname: Junot
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Roméo
mesh_terms: D000328:Adult; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D019803:Glutathione Disulfide / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D055442:Metabolome; D009154:Mutation; D018384:Oxidative Stress
chemical_list: D001798:Blood Proteins; D008562:Membrane Glycoproteins; C498523:RHAG protein, human; D019803:Glutathione Disulfide