Haemochromatosis in patients with beta-thalassaemia trait

Severe iron overload has been reported in patients with the beta -thalassae mia trait. Studies performed before the discovery of the haemochromatosis g ene (HFE) have yielded conflicting results: some suggest that iron overload might arise from the interaction of the beta -thalassaemia trait with hete rozygosity for haemochromatosis, some with homozygosity for haemochromatosi s and others that it was unrelated to haemochromatosis. We have studied the clinical phenotype, iron indices and HFE genotypes of 22 unrelated patient s with the beta -thalassaemia trait and haemochromatosis, the inheritance o f chromosome 6p and 1q haplotypes in families of non-homozygous C282Y proba nds and serum measures of iron status in relatives heterozygous for C282Y w ith or without the beta -thalassaemia trait. We demonstrate that the beta - thalassaemia trait aggravates the clinical picture of C282Y homozygotes, fa vouring higher rates of iron accumulation and the development of severe iro n-related complications. We suggest that the coexistence of the beta -thala ssaemia trait might also increase the risk of iron overload in patients wit h HFE genotypes at a mild risk of haemochromatosis. Our findings do not sup port the hypothesis that the association of the beta -thalassaemia trait wi th a single C282Y or H63D allele might lead to iron overload and suggest th at other non-HFE-related inherited factors are present in haemochromatosis patients with incomplete HFE genotypes.