The influence of hemochromatosis mutations on iron overload of thalassemiamajor

Background and Objective. Hemochromatosis is a genetic form of iron overloa d due to a defective HFE gene. Secondary iron overload is the main complica tion in transfusion-dependent thalassemia patients. In this work we have ex amined the prevalence of HFE mutations in thalassemia major and evaluated t he degree of iron overload of patients with and without HFE mutations. Design and Methods. HFE mutations were studied in 71 Italian thalassemic pa tients and in 189 normal controls, using PCR and restriction enzyme analysi s. The degree of iron overload, assessed by serum ferritin and liver iron c oncentration (LIC), was compared in 17 patients with mutations in the HFE g ene, and in II subjects with wild type HFE genotype. The two groups of pati ents had comparable globin gene mutations, were matched for age and were ho mogeneous for transfusion and chelation history. In all cases the iron bala nce calculated on the basis of transfusion regimen and iron excreted by che lation was avail able. Results. The allele frequencies of C282Y and H63D were respectively 1.4% an d 12.7% in patients and 1.1% and 11.4% in controls. No case of C282Y homozy gosity was recorded among patients. No significant difference was found in terms of serum ferritin, LIC, or the age at chelation start between patient s with and without HFE mutations. The single patient with H63D homozygosity was severely iron-loaded. Interpretation and Conclusions. Our data suggest that the presence of a sin gle mutation in the HFE gene does not influence the severity of iron loadin g in thalassemia patients following a regular transfusion and chelation pro gram. (C) 1999, Ferrata Storti Foundation.