HFE gene mutation (C282Y) and phenotypic expression among a hospitalised population in a high prevalence area of haemochromatosis

Background-Previous studies have shown that up to 0.5% of the Caucasian pop ulation is homozygous for the HFE gene C282Y mutation. High prevalence valu es have been reported in Northern Europe. To what extent the presence of th is mutation is associated with overt clinical haemochromatosis is unclear. Aim-To determine the prevalence of the C282Y allele in a hospitalised popul ation of an acute medical department, and study the phenotypic expression i n the homozygotes. Methods-Blood samples were obtained from 2027 hospitalised patients; 1900 C aucasians and 127 non-Caucasians. Serum iron, transferrin, and ferritin wer e measured at admission. The presence of the HFE gene mutation was determin ed by polymerase chain reaction based analysis. Follow up fasting blood sam ples were obtained from patients homozygous for the mutation. Results-Fourteen of the 1900 Caucasian subjects (0.74%) were homozygous and 224 (11.8%) were heterozygous for the C282Y mutation, including 32 subject s (1.7%) who were compound heterozygous for the C282Y and H63D mutations. T en of 14 (71%) homozygous patients displayed mild to moderate biochemical e xpression of haemochromatosis with a serum ferritin level <550 mu g/l, two (14%) patients were "non expressing", and two of five in whom liver biopsie s were carried out had cirrhosis, including one with advanced hepatocellula r carcinoma. Conclusions-The prevalence of C282Y homozygosity in a hospitalised populati on was 0.74%. However, the majority of homozygous patients displayed mild t o moderate biochemical expression. C282Y mutation screening may detect indi viduals that do not develop haemochromatosis. Transferrin saturation and fe rritin, which are used as first line screening in haemochromatosis, may be highly unreliable in the presence of an inflammatory process.