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Variation of iron loading expression in C282Y homozygous haemochromatosis probands and sib pairs
  1. Catherine Mura,
  2. Gérald Le Gac,
  3. Virginie Scotet,
  4. Odile Raguenes,
  5. Anne-Yvonne Mercier,
  6. Claude Férec
  1. Centre de Biogénétique, ETSBO, CHU, UBO, BP454, 46 rue Félix Le Dantec, F-29275 Brest, France
  1. Dr Mura, Catherine.Mura{at}

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Editor—Hereditary haemochromatosis (HH), a common autosomal recessive disease of iron metabolism, is more prevalent among populations of northern Europe with an affected rate of 1 in 200 to 400 and a carrier frequency of around 1 in 10.1 2 The disease is characterised by progressive iron overload, and the clinical onset usually appears after middle age. The phenotypic manifestations of HH are variable, and the severity of the disease is related to the iron loading; the most common symptoms of iron overload are fatigue, lethargy, arthropathy, and skin pigmentation, often along with more serious organ damage including cirrhosis, diabetes mellitus, myocardiopathy, and endocrine dysfunction. The assessment of iron loading is currently based on the levels of biochemical iron markers such as transferrin saturation percentage, serum ferritin, and serum iron concentrations. However, the diagnosis of haemochromatosis can now be confirmed using direct HFE mutation testing. The prognosis depends on early diagnosis and therapeutic venesections. Thus, population screening would allow early diagnosis during the asymptomatic phase and prophylactic treatment by repeated venesection to prevent the irreversible damage of iron overload,3 but predictive diagnosis requires a well established phenotype-genotype correlation.

The identification of the haemochromatosis gene,4 now referred to as HFE,5 enables the performance of direct genetic testing for diagnosis. The role of the HFE protein in iron metabolism has not yet been clearly established, but it seems that the complex of HFE with β2-microglobulin interacts with the transferrin receptor (TfR) on the cell surface, which decreases the affinity of TfR for transferrin.6-9 Some mutations characterised in theHFE gene and leading to a functional defect have been correlated with HH. Two missense mutations, 845G→A (C282Y) accounting for 80-90% of HH chromosomes,4 10-13 and 187C→G, (H63D) representing 40-70% of non-C282Y HH chromosomes,4 12-15 leading …

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