HFE gene mutations in Brazilian thalassemic patients

Abstract

Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron intake and progressive storage and is related to mutations in the HFE gene. Interactions between thalassemia and hemochromatosis may further increase iron overload. The ethnic background of the Brazilian population is heterogeneous and studies analyzing the simultaneous presence of HFE and thalassemia-related mutations have not been carried out. The aim of this study was to evaluate the prevalence of the H63D, S65C and C282Y mutations in the HFE gene among 102 individuals with alpha-thalassemia and 168 beta-thalassemia heterozygotes and to compare them with 173 control individuals without hemoglobinopathies. The allelic frequencies found in these three groups were 0.98, 2.38, and 0.29% for the C282Y mutation, 13.72, 13.70, and 9.54% for the H63D mutation, and 0, 0.60, and 0.87% for the S65C mutation, respectively. The chi-square test for multiple independent individuals indicated a significant difference among groups for the C282Y mutation, which was shown to be significant between the beta-thalassemia heterozygote and the control group by the Fisher exact test (P value = 0.009). The higher frequency of inheritance of the C282Y mutation in the HFE gene among beta-thalassemic patients may contribute to worsen the clinical picture of these individuals. In view of the characteristics of the Brazilian population, the present results emphasize the need to screen for HFE mutations in beta-thalassemia carriers.

Cord blood transplantation in a young child with pyruvate kinase deficiency

“…Secondary hemochromatosis from iron overload has been documented in occasional non‐transfused patients with PK deficiency. Some patients with PK deficiency have concomitant HFE mutation, although the present patient did not have any of the three mutations (C282Y, H63D, or S65C) observed in > 95% of patients with hereditary hemochromatosis . Furthermore, the present patient did have hemochromatosis as observed on liver biopsy.…”

“…Some patients with PK deficiency have concomitant HFE mutation, 8 although the present patient did not have any of the three mutations (C282Y, H63D, or S65C) observed in > 95% of patients with hereditary hemochromatosis. 4 Furthermore, the present patient did have hemochromatosis as observed on liver biopsy. The etiology of iron overload was diagnosed as secondary hemochromatosis and was due to repeated RBC transfusions.…”

“…Liver biopsy showed periportal lymphocyte infiltration, mild fibrosis surrounding hepatic cells, and iron deposits in Kupffer cells and hepatic cytoplasm, corresponded to the finding of mild hemochromatosis. The hemochromatosis (HFE) gene for hemochromatosis, however, did not contain any mutations as described by Oliveira et al 4 Thereafter, liver dysfunction improved on treatment with ursodeoxycholic acid and vitamins, and AST and ALT hovered around 100 IU/L, and ferritin around 400 ng/mL without iron-chelating therapy. Although the patient received monthly transfusions, she was unable to maintain hemoglobin >5 g/dL.…”

“…Liver biopsy showed periportal lymphocyte infiltration, mild fibrosis surrounding hepatic cells, and iron deposits in Kupffer cells and hepatic cytoplasm, corresponded to the finding of mild hemochromatosis. The hemochromatosis ( HFE ) gene for hemochromatosis, however, did not contain any mutations as described by Oliveira et al …”

Inherited haemochromatosis with C282Y mutation in a patient with alpha-thalassaemia: a treatment dilemma

“…Otherwise, the patient would receive blood transfusion or iron with all its possible complications and hazards to improve Hb along with chelating agent to prevent iron overload 9 12. A study conducted by Oliveira and colleagues1 had evaluated the presence of C282Y (hereditary haemochromatosis) among 102 patients with alpha-thalassaemia. Only one patient had demonstrated C282Y gene with percentage of 0.98%.…”