In 1996, Feder and colleagues1 showed that homozygosity fora mutation (C282Y) in the HFE gene is responsible for the majorityof cases of typical phenotypic hereditary hemochromatosis. Atthat time, it was commonly believed that most C282Y homozygoteswould have progressive iron loading and disease manifestationsresulting from iron overload. This assumption of high clinicalpenetrance was based on numerous studies of patients with symptomatichereditary hemochromatosis, who had a high incidence of diseasecharacteristics, including liver disease (fibrosis, cirrhosis,and hepatocellular cancer), characteristic arthropathy involvingthe second and third metacarpophalangeal joints, diabetes, andother endocrine manifestations.2
From the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis.
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