Results of many studies from around the world have revealed that haemochromatosis is the most prevalent genetic disease in people of European descent. However, it continues to be regarded as an uncommon disease by many physicians and is not listed as a common cause of death. The gene for haemochromatosis was discovered in 1996 and most typical patients are homozygous for the C282Y mutation of the HFE gene.1 Studies using genetic testing have estimated the prevalence to be in the 1:188 to 1:327 range (table1).2-5 The two most likely explanations for the apparent discrepancy between prevalence studies of haemochromatosis and the clinical impression are: (a) the failure to consider the diagnosis and to order the appropriate diagnostic tests (underdiagnosis) and (b) absence of iron overload and clinical disease in patients homozygous for the haemochromatosis gene (incomplete penetrance).

The percentage of C282Y homozygotes with iron overload as defined by an increased serum ferritin in population screening studies has ranged from 19% (blood donors) to 75% in the general population (table 1). However, an elevated serum ferritin is not synonymous with the inevitable progression of the disease to cirrhosis, diabetes, heart disease, and other haemochromatosis related morbidity. In a study of patients with haemochromatosis from our hospital, treated at the time of diagnosis and followed over a 30 year period, 43% of men and 28% of women developed life threatening complications.6 This is likely to be an overestimate of the morbidity of haemochromatosis because of a referral bias. A major impediment in the implementation of population screening for haemochromatosis has been this uncertainty about the burden of disease and the natural history of disease in an asymptomatic C282Y homozygote detected by screening. The unique design of the …