Screening for hemochromatosis: phenotype versus genotype

Abstract

Hereditary hemochromatosis is one of the most common inherited disorders among Caucasians of European ancestry. Malregulation of iron absorption from the duodenum eventually leads to iron overload. Although the time required to become iron loaded is variable, it is clear that most homozygotes will eventually become symptomatic. The clinical manifestations can be prevented by prophylactic phlebotomy therapy. Screening young populations is therefore a key to the prevention of disease-related morbidity. Protocols based on the phenotype of high transferrin saturation already exist. The recent identification of a candidate gene for hemochromatosis now allows for a potential genetic screen. Both the phenotypic and the genotypic methods of screening have inherent advantages and disadvantages. Iron-depletion therapy of homozygotes before the development of disease-related morbidity results in normal longevity. National initiatives for hemochromatosis screening will prevent morbidity by identifying and treating young, healthy homozygotes. Healthy, iron-depleted homozygotes should be eligible for health and life insurance at standard rates. Furthermore, healthy homozygotes would make ideal blood donors.