Hemochromatosis

Synonyms

Hanot-Chauffard syndrome; Iron overload

Definition

Hemochromatosis is a systemic disorder of iron overload leading to eventual organ dysfunction.

Etiology

Primary hemochromatosis is the most common type of hemochromatosis and is due to autosomal recessive missense mutations on short arm of chromosome 6 in HFE. This gene encodes for an MHC class 1-like molecule that binds with transferrin receptor and affects hepcidin homeostasis. The subsequent defect of this pathway leads to increased iron absorption in the upper gastrointestinal tract, leading to iron deposition in parenchymal cells of the liver, heart, pancreas, joints, and endocrine organs.

The C282Y mutation is the most frequently identified causative genetic lesion, for which homozygosity confers the disease state. Patients heterozygous for this allele are carriers but generally do not demonstrate clinical disease. The exception is the compound heterozygote; carriers who also have the H63D mutation, prevalent among...