Hemochromatosis is an iron overload disorder caused by the excess storage of iron in the body, which may lead to organ damage.  Hereditary hemochromatosis (HH) is one of the most common genetic disorders, and is most prevalent in adult males of northern European descent.  HH has been linked to a number of variants in several genes related to iron regulation.  The severity of the causative variant correlates with the time course of iron overload and organ damage; more severe variants lead to pediatric onset of symptoms, while less severe variants may lead to adult symptom onset, or may never result in symptoms. The most common form of adult HH has been linked to variants (C282Y, H63D, and S65C) of the HFE gene, which codes for a protein responsible for iron regulation.   Pediatric HH is rare.  The majority of pediatric cases are linked to variants of the HFE2 gene, which codes for hepcidin.  Initial testing for hemochromatosis involves assessment of iron overload via serum transferrin saturation, which is calculated from serum iron and iron binding capacity, and serum ferritin testing. Genetic testing for HFE HH is indicated if biochemical or clinical findings are suggestive, and is recommended for adult family members of individuals with a homozygous C282Y genotype  and for reproductive partners of individuals diagnosed with HFE HH.  Once HFE HH is diagnosed, ongoing monitoring of iron status is required, particularly if venesection or blood donation is used to control iron overload.

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Content Review: 
March 2019

Last Update: March 2019