Hereditary hemochromatosis - Impact of molecular and iron-based testing onthe diagnosis, treatment, and prevention of a common, chronic disease

Objective.-To review the current state-of-the-art regarding the role of iro n- and DNA-based testing on the detection, treatment, and prevention of her editary hemochromatosis (HH), the most common single-gene disorder in white people. Sources.-Review of the medical literature, with particular emphasis on rece nt reports of the impact of DNA-based testing on the detection of symptomat ic and presymptomatic patients with HH. Conclusions.-Hereditary hemochromatosis, a common autosomal recessive iron overload disorder (with a population prevalence of 0.3%-0.8%), is a common cause of preventable liver, heart, joint, and endocrine disease. Since the associated clinical signs and symptoms are nonspecific, an accurate HH diag nosis demands both a high index of suspicion and the direct laboratory demo nstration of elevated iron parameters, The substantial public health burden of HH as a common, deadly, detectable, and treatable chronic disease has l ed the College of American Pathologists to recommend that "systematic scree ning for hemochromatosis is warranted for all persons over the age of 20 ye ars." The recent discovery that most HH cases are the result of a single we ll-conserved homozygous missense mutation (C282Y) within a novel transferri n-receptor binding protein (HFE) has given rise to diagnostic clinical test s for the DNA-based detection of this pathologic mutation. This direct HFE mutation test can now be used not only to confirm the diagnosis of HH in th ose with symptomatic disease, but also, perhaps more importantly, to detect those with presymptomatic iron overload in whom future disease manifestati ons may be prevented (with phlebotomy therapy).