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Genetic hemochromatosis (GH) is believed to be a disease restricted to those of European ancestry. In northwestern Europe, >80% of GH patients are homozygous for one mutation, the substitution of tyrosine for cysteine at position 282 (C282Y) in the unprocessed protein. In a proportion of GH patients, two mutations are present, C282Y and H63D. The clinical significance of this second mutation is such that it appears to predispose 1%-2% of compound heterozygotes to expression of the disease. The distribution of the two mutations differ, C282Y being limited to those of northwestern European ancestry and H63D being found at allele frequencies>5%, in Europe, in countries bordering the Mediterranean, in the Middle East, and in the Indian subcontinent. The C282Y mutation occurs on a haplotype that extends

Severe forms of anemia in children in the developing countries may be characterized by different clinical manifestations at particular stages of development. Whether this reflects developmental changes in adaptation to anemia or other mechanisms is not clear. The pattern of adaptation to anemia has been assessed in 110 individuals with hemoglobin (Hb) E ␤-thalassemia, one of the commonest forms of inherited anemia in Asia. It has been found that age and Hb levels are independent variables with respect to erythropoietin response and that there is a decline in the latter at a similar degree of anemia during development. To determine whether this finding is applicable to anemia due to other causes, a similar study has been carried out on 279 children with severe anemia due to Plasmodium falciparum malaria; the results were similar to those in the patients with thalassemia. These observations may have important implications both for the better understanding of the pathophysiology of profound anemia in early life and for its more logical and cost-effective management.erythropoietin ͉ malaria ͉ thalassemia ͉ hemoglobin

Hemoglobin E ␤ thalassemia is the commonest form of severe thalassemia in many Asian countries. Its remarkably variable clinical phenotype presents a major challenge to determining its most appropriate management. In particular, it is not clear why some patients with this condition can develop and function well at very low hemoglobin levels. Here, we demonstrate that patients with hemoglobin E␤ thalassemia have a significant decrease in the oxygen affinity of their hemoglobin, that is an increased P 50 value, in response to anemia. This may in part reflect the lower level of hemoglobin F in this condition compared with other forms of ␤ thalassemia intermedia. The ability to rightshift the oxygen dissociation curve was retained across the spectrum of mild and severe phenotypes, despite the significantly higher levels of hemoglobin F in the former, suggesting that efforts directed at producing a modest increase in the level of hemoglobin F in symptomatic patients with this disease should be of therapeutic value. (Blood. 2010;116(24): 5368-5370)