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Articles free to read on publisher website Hereditary haemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism common in populations of north-west European ancestry. The term haemochromatosis was first used by von Recklinghausen (1889) to describe his post-mortem findings in patients who had died from ‘bronzed diabetes’. The condition was first suggested to be familial by Sheldon (1935), although it was as late as 1975 before the genetic nature of the condition was proven, when Simon et al (1975 ) demonstrated association with the HLA-A3 allele in the major histocompatibility complex (MHC) on chromosome 6...

Free to read on publisher website We thank Fairbanks et al for their comments and agree with their conclusion that the H63D mutation may be associated with iron accumulation. This is supported by the recent finding that the HFE protein with the H63D mutation does not reduce the affinity of transferrin for its receptor in the same way as the wild type protein. 1 However, we have reservations about combining data from various groups of patients and controls where the frequency of the mutations in the general population varies greatly...

BACKGROUND The diagnosis of genetic haemochromatosis (GH) before iron overload has developed is difficult. However a convincing candidate gene for GH, HFE (previously HLA-H), has been described recently. AIMS To determine the prevalence of the haemochromatosis associated HFE mutations C282Y and H63D in United Kingdom affected and control populations. METHODS The prevalence of the HFE C282Y and H63D mutations was determined by polymerase chain reaction amplification and restriction enzyme digestion in a cohort of 115 well characterised patients with GH and 101 controls from the United Kingdom. RESULTS One hundred and five of 115 (91%) patients with GH were homozygous for the C282Y mutation. Only one of 101 (1%) controls was homozygous for the C282Y mutation and this individual currently shows evidence of iron overload. Two of five patients who did not have either of the two described mutations of HFE had early onset iron overload (ages 16 and 24). One had a family history of cardiac failure and the second was subsequently hospitalised due to cardiac failure. These are the first phenotypic observations for patients without either C282Y or H63D mutation of HFE. CONCLUSION This simple genetic test promises to be a highly effective tool in the diagnosis of GH.