The clinical expression of hemochromatosis in Oslo, Norway - Excessive oral iron intake may lead to secondary hemochromatosis even in HFE C282Y mutation negative subjects

Background: The prevalence of hereditary hemochromatosis in Norway is one o f the highest reported in the world. However, the clinical presentation in patients with hemochromatosis in Norway seems to be different compared with recent studies elsewhere. The aim of this study was to investigate patient s with hemochromatosis in one community hospital in Norway and to study the prevalence of the C282Y mutation. Methods: One hundred and twenty patients were consecutively admitted to one medical department in Oslo. Serum trans ferrin and ferritin concentrations were measured in all patients, and a per cutaneous liver biopsy was obtained in 108 of 120 (90%) patients. Stainable iron (Perls stain) in hepatocytes was graded from 0 to 4+ and fibrosis fro m 1 to 4. Genotyping for the C282Y and H63D mutation in the HFE gene was pe rformed by PCR-RFLP. Results: Forty-eight (40%) of the patients suffered fr om tiredness and astenia and 29 (24%) had typical arthropathy. Only 5 of 10 5 (4.5%) had biopsy confirmed cirrhosis and 5 had diabetes mellitus. Patien ts referred from a blood bank had significantly less symptoms and signs com pared with other patients. Twenty-one of 120 (17.5%) patients were C282Y mu tation negative. Seventeen (81%) of these patients (16 women and 1 man) had a history of extensive oral iron intake lasting from 5 to 50 years. When e xcluding those with extensive oral iron intake (n = 17), 92 of 103 (89%) we re homozygous for the C282Y mutation, 7 (7%) were heterozygous including 3 compound heterozygous and 4 (4%) were mutation negative. Conclusions: Only a minority of our patients with hemochromatosis had a far advanced disease at the time of diagnosis (less than 5% had cirrhosis) and hemochromatosis i n a majority of the C282Y mutation negative patients was associated with ex cessive oral iron intake for several years.