Screening for hemochromatosis: patients with liver disease, families, and populations

Hereditary hemochromatosis is a common autosomal- recessive disorder of iron overload usually occurring in individuals who are homozygous for a C282Y mutation in the hemochromatosis (HFE) gene. Current screening methods can detect affected individuals early in disease pathogenesis, enabling early institution of effective treatment that can restore normal life expectancy. Phenotypic screening of adults using transferrin saturation and serum ferritin levels identifies the majority of individuals who develop iron overload. HFE genotyping, when combined with serum biochemical measurements, has reduced reliance on liver biopsy as a diagnostic tool and is the preferred initial screening modality for families with an affected individual. Genetic testing has altered previously held views regarding the high level of penetrance of the disease. Although the majority of C282Y homozygotes develop increased body iron stores, end-organ damage occurs much less frequently than previously thought. Screening is recommended in high-risk groups and in those with a high index of clinical suspicion. Opportunistic screening during routine health assessments may also be recommended. However, large-scale screening of the average-risk population is not recommended on the basis of current evidence.