Haemochromatosis in patients with β‐thalassaemia trait

Severe iron overload has been reported in patients with the β‐thalassaemia trait. Studies performed before the discovery of the haemochromatosis gene (HFE) have yielded conflicting results: some suggest that iron overload might arise from the interaction of the β‐thalassaemia trait with heterozygosity for haemochromatosis, some with homozygosity for haemochromatosis and others that it was unrelated to haemochromatosis. We have studied the clinical phenotype, iron indices and HFE genotypes of 22 unrelated patients with the β‐thalassaemia trait and haemochromatosis, the inheritance of chromosome 6p and 1q haplotypes in families of non‐homozygous C282Y probands and serum measures of iron status in relatives heterozygous for C282Y with or without the β‐thalassaemia trait. We demonstrate that the β‐thalassaemia trait aggravates the clinical picture of C282Y homozygotes, favouring higher rates of iron accumulation and the development of severe iron‐related complications. We suggest that the coexistence of the β‐thalassaemia trait might also increase the risk of iron overload in patients with HFE genotypes at a mild risk of haemochromatosis. Our findings do not support the hypothesis that the association of the β‐thalassaemia trait with a single C282Y or H63D allele might lead to iron overload and suggest that other non‐HFE‐related inherited factors are present in haemochromatosis patients with incomplete HFE genotypes.

[1]  G. Mancia,et al.  Two novel nonsense mutations of HFE gene in five unrelated italian patients with hemochromatosis. , 2000, Gastroenterology.

[2]  Paolo Gasparini,et al.  The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22 , 2000, Nature Genetics.

[3]  N. Andrews,et al.  Genes that modify the hemochromatosis phenotype in mice. , 2000, The Journal of clinical investigation.

[4]  M. Cappellini,et al.  Hemochromatosis: Thalassemias and their interactions with hemochromatosis , 2000 .

[5]  P. Gasparini,et al.  Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. , 1999, The New England journal of medicine.

[6]  K. Do,et al.  Linkage disequilibrium analysis in Australian haemochromatosis patients indicates bipartite association with clinical expression. , 1999, Journal of hepatology.

[7]  J. Dooley,et al.  A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote. , 1999, Gastroenterology.

[8]  J. Barton,et al.  Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. , 1999, Blood cells, molecules & diseases.

[9]  M. Cazzola,et al.  Juvenile hemochromatosis locus maps to chromosome 1q. , 1999, American journal of human genetics.

[10]  C. Camaschella,et al.  Inherited HFE‐unrelated hemochromatosis in italian families , 1999, Hepatology.

[11]  W. Sly,et al.  Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  C. Férec,et al.  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS HFE Mutations Analysis in 711 Hemochromatosis Probands: Evidence for S65C Implication in Mild Form of Hemochromatosis , 2016 .

[13]  M. Cappellini,et al.  NONTRANSFUSIONAL IRON OVERLOAD IN THALASSEMIA INTERMEDIA : ROLE OF THE HEMOCHROMATOSIS ALLELE , 1998 .

[14]  V. Gürtler,et al.  Aetiology of severe iron overload in a family with hereditary haemolytic anaemia , 1998, British journal of haematology.

[15]  D. Girelli,et al.  Heterogeneity of hemochromatosis in Italy. , 1998, Gastroenterology.

[16]  D. M. Penny,et al.  The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. Pietrangelo,et al.  Molecular genetics and control of iron metabolism in hemochromatosis. , 1998, Haematologica.

[18]  E. Beutler,et al.  New diallelic markers in the HLA region of chromosome 6. , 1997, Blood cells, molecules & diseases.

[19]  D. Girelli,et al.  Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. , 1997, American journal of human genetics.

[20]  M. C. Ellis,et al.  A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis , 1996, Nature Genetics.

[21]  D. Girelli,et al.  The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients , 1996, Hepatology.

[22]  M. Pippard,et al.  Erythrokinetics and iron status in heterozygous β thalassaemia, and the effect of interaction with α thalassaemia , 1987 .

[23]  S. Fargion,et al.  Iron overload in subjects with beta‐thalassaemia trait: role of idiopathic haemochromatosis gene , 1985, British journal of haematology.

[24]  P. Parfrey,et al.  Iron overload in beta-thalassaemia minor. A family study. , 2009, Scandinavian journal of haematology.

[25]  M. Skolnick,et al.  Coincidental nontransfusional iron overload and thalassemia minor: association with HLA-linked hemochromatosis. , 1981, Blood.

[26]  C. Williams,et al.  Hemosiderosis in association with thalassemia minor. , 1968, Archives of internal medicine.

[27]  E. Huehns,et al.  Thalassaemia Minor Complicated by Excessive Iron Storage , 1963, British journal of haematology.

[28]  A. R. Muir,et al.  Hepatic pathology in relatives of patients with haemochromatosis. , 1962, The Journal of pathology and bacteriology.