Haemochromatosis

Published on 05/05/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

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116 Haemochromatosis

Advanced-level questions

Does this disease run in families?

Yes, and it is an autosomal recessive condition. At least four different genes encoding proteins involved in iron metabolism have been described: HJV, HAMP, TfR2 and HFE. HFE is on chromosome 6. Two mutations (845A (C282Y) and 187C (H63D)) account for 90% of cases in those of European extraction. HFE is closely associated with HLA-A3 and to a lesser extent with HLA-B14. The responsible alleles are on the short arm of chromosome 6 (Nat Genet 1996;13:399–408). Asymptomatic close relatives of patients with hereditary haemochromatosis, in particular siblings, should be advised to undergo screening (measurements of serum ferritin and iron, and saturation of iron-binding capacity). Hereditary haemochromatosis can occur in adults who do not have pathogenic mutations affecting chromosome 6 (N Engl J Med 1999;341: 718–24, 725–32). A substantial number of homozygous relatives of these patients (more commonly men) have disease-related conditions such as cirrhosis, hepatic fibrosis, elevated amiotransferase and haemochromatotic arthropathy that may not have been detected clinically (N Engl J Med 2000;343:1529–35).

However, 10% or more of the patients with clinically severe hereditary haemochromatosis do not have these mutations and this limits the value of diagnostic DNA testing. Ferroportin-associated iron overload, currently classified as hereditary haemochromatosis type 4, was clinically recognized in 1999 and was linked to SLC40A1, which encodes ferroportin, a protein involved in cellular iron export.