Methemoglobinemia and ascorbate deficiency in hemoglobin E beta thalassemia: metabolic and clinical implications

作者：Allen Angela; Fisher Christopher; Premawardhena Anuja; Bandara Dayananda; Perera Ashok; Allen Stephen; St Pierre Timothy; Olivieri Nancy; Weatherall David^*

来源：Blood, 2012, 120(15): 2939-2944.

DOI：10.1182/blood-2012-06-435875

During investigations of the phenotypic diversity of hemoglobin (Hb) E beta 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 beta 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. (Blood. 2012; 120(15): 2939-2944)

• 出版日期2012-10-11