title: Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabolic and clinical implications.
abstract: During investigations of the phenotypic diversity of hemoglobin (Hb) E β thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE β thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population. There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective.
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Allen
authors.forename: Christopher
authors.initials: C
authors.lastname: Fisher
authors.forename: Anuja
authors.initials: A
authors.lastname: Premawardhena
authors.forename: Dayananda
authors.initials: D
authors.lastname: Bandara
authors.forename: Ashok
authors.initials: A
authors.lastname: Perera
authors.forename: Stephen
authors.initials: S
authors.lastname: Allen
authors.forename: Timothy
authors.initials: T
authors.lastname: St Pierre
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.forename: David
authors.initials: D
authors.lastname: Weatherall
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000378:metabolism*; D001206:Ascorbic Acid Deficiency / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005190:Family; D005260:Female; D006446:Hemoglobin E / Q000378:metabolism*; D006801:Humans; D008297:Male; D008706:Methemoglobin / Q000378:metabolism*; D008708:Methemoglobinemia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications* / Q000378:metabolism
chemical_list: D008706:Methemoglobin; D006446:Hemoglobin E; D001205:Ascorbic Acid