Introduction

Hemochromatosis is an inherited disease characterized by excessive absorption of dietary iron leading to progressive tissue iron accumulation and ultimately organ damage. Early diagnosis and appropriate management can prevent disease manifestations. The high prevalence of this disorder makes it a logical target for routine screening. Hemochromatosis is generally viewed as a relatively uncommon disorder. However, several recent studies estimate its prevalence to be 3–8 per 1000, making it one of the most common genetic disorders. These high prevalence figures have been derived largely by screening asymptomatic individuals using serum transferrin saturation (TS), serum ferritin (SF) concentrations, or a combination of these tests. Hemochromatosis is an autosomal recessive disorder, the gene for which is linked to the histocompatibility (HLA) loci on the short arm of chromosome 6. Recently, a single amino acid mutation (C282Y) in a gene on chromosome 6, designated HFE, has been described, and appears to account for approximately 83% of cases of hemochromatosis. Another 4% of affected individuals are compound heterozygotes for the C282Y mutation and for another mutation in the same gene (H63D). The mechanism by which these mutations result in iron overload is unclear (see Fig. 51.1).

Hemochromatosis has been defined as homozygosity for the mutant allele. With the description of the HFE gene, it is clear that there may be genetic defects that result in iron overload in some cases. Persons homozygous for the hemochromatosis allele(s) do not have increased iron stores early in life.