Diagnosis:
Hereditary Hemochromatosis
• The patient in the scenario most likely has hereditary hemochromatosis, but iron overload also can be seen in the setting of thalassemia, multiple blood transfusions, and hemolytic anemia. Hereditary hemochromatosis is a homozygous autosomal recessive disorder resulting from mutations in the HFE gene. The most common mutation is C282Y, which is present in 70% to 100% of patients with this diagnosis. The HFE gene is responsible for encoding the HFE protein, which is normally expressed in small intestinal cells and is important in the regulation of iron uptake into the cell. The mutant protein results in unregulated uptake of iron regardless of systemic iron content.
• The biopsy specimen shows myocytes and interstitial macrophages containing abundant intracellular brown pigment, which would prove to be iron if stained with Prussian blue and is diagnostic of iron overload.
• It is important not to confuse this pigment with lipofuscin, which is a pigment of granules of undigested material derived from intracellular lipid peroxidation. Lipofuscin granules are more finely granular than hemosiderin and accumulate in the cytoplasm of many cell types over time. However, unless there has been a prior infarct or other myocardial damage, there would not be significant lipofuscin in interstitial macrophages.
• Iron deposition in the liver, pancreas, heart, pituitary, and skin results in clinical manifestations such as hepatomegaly, diabetes, cardiomyopathy, amenorrhea, and hyperpigmentation.
• The treatment of hemochromatosis consists of regular phlebotomy.
• A more recent study showed little correlation between the quantity of cardiac iron deposition and systolic dysfunction in patients with hemochromatosis. Of eight patients who showed improved cardiac function with phlebotomy, three had no demonstrable cardiac iron.
