Key Points
����Hereditary hemochromatosis (HH) remains the most common identified
genetic disorder in Caucasians.
����The principal defect is a point mutation in the hemochromatosis gene (HFE)
that produces the C282Y protein leading to excess dietary iron absorption.
C282Y homozygotes account for 80%-85% of typical patients with HH with
a small minority who are C282Y/H63D compound heterozygotes.
����Although its geographic distribution is worldwide, HH is seen most
commonly in populations of northern European origin, particularly Nordic or
Celtic ancestry, in which it occurs with a prevalence of approximately 1 per
220-250 individuals.
����HH may lead to the development of life-threatening complications���
cirrhosis, hepatocellular carcinoma (HCC), diabetes, and heart disease.
����Phenotypic expression occurs in approximately 70% of C282Y homozygotes,
but fewer than 10% of C282Y homozygotes will develop severe iron
overload accompanied by organ damage and clinical manifestations of
hemochromatosis.
����In 2000, The European Association for the Study of Liver Diseases defined
three stages of HH to allow clinicians to categorize patients who have
positive genetic test results:
������ Stage 1: Patients with the genetic disorder with no increase in iron stores.
������ Stage 2: Patients with the genetic disorder who have phenotypic evidence of iron
overload but who are without tissue or organ damage.
������ Stage 3: Patients who have the genetic disorder with iron overload and have iron
deposition to the degree that tissue and organ damage occurs.
