1. Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabolic and clinical implications
- Author
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Timothy G. St. Pierre, Stephen Allen, David J. Weatherall, Anuja Premawardhena, Chris Fisher, Angela Allen, Ashok Perera, Nancy F. Olivieri, and Dayananda Bandara
- Subjects
Adult ,Male ,medicine.medical_specialty ,Anemia ,Thalassemia ,Immunology ,Plenary Paper ,Ascorbic Acid ,Biology ,Methemoglobinemia ,Biochemistry ,Methemoglobin ,Young Adult ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Family ,Hemoglobin E ,beta-Thalassemia ,Haptoglobin ,Beta thalassemia ,Cell Biology ,Hematology ,medicine.disease ,Endocrinology ,Ascorbic Acid Deficiency ,biology.protein ,Female ,Hemoglobin - 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.
- Published
- 2012