Nontransfusional Iron Overload in Thalassemia: Association with Hereditary Hemochromatosis

Obscure pathogenesis of primary iron overload in Indians warrants more focused research

“…Neither the patients with heterozygous H63D mutation, nor the lone compound heterozygote individual (C282Y/H63D) had primary iron overload. These observations are in concordance with previous studies from India where C282Y has not been identified except for a single individual from Punjab in northern India, and a more widespread distribution of H63D mutation has been reported [4][5][6][7][8]. The H63D mutation is widely distributed in nearly all populations with a variable allele frequency and haplotype analysis suggests that it has occurred earlier to the C282Y mutation.…”

Beta-thalassemia

“…Some studies seem to indicate that the common mutation of the HFE gene (C282Y), which causes the common type of HH, might be involved in determining the variability of iron overload in patients with thalassemia intermedia. 80 Longo et al 81 by studying a large group of thalassemia major patients found that the presence of a single mutation in HFE gene (C282Y and H63D) does not influence the severity of iron loading, assessed by serum ferritin and liver iron concentration, likely because the effect of the mutations on iron overload is hidden as a result of treatment (i.e., posttransfusional iron overload and iron chelation). Furthermore, homozygosity for the H63D mutation, whose functional significance in HH is still being evaluated, when coinherited with heterozygous betathalassemia seems to determine an increase in iron overload.…”

HFE gene mutations in Brazilian thalassemic patients

“…This hypothesis indicates that beta-thalassemia carriers might exhibit an advantage in balancing iron storage in their organisms. Nevertheless, published data indicate more severe hemochromatosis symptoms when heterozygosis for the C282Y mutation is associated with beta-thalassemia (19), and when higher serum iron levels in beta-thalassemia co-inheritance are associated with heterozygosis and homozygosis for H63D (4,26). However, these results remain controversial (29,31).…”

“…If transfusions are needed, they will add to the body iron excess. The interaction of the HH mutations with the thalassemias may have a synergistic effect, increasing the iron intake and storage (19,20).…”