Hemochromatosis
Hemochromatosis is a disorder of iron overload, most often hereditary HFE C282Y homozygosity causing hepcidin deficiency and excess intestinal iron absorption, that deposits iron in the liver, pancreas, heart, joints, skin, and pituitary. Screening rests on fasting transferrin saturation and ferritin, confirmation on HFE genetic testing, and treatment on regular therapeutic phlebotomy to a target ferritin of 50 to 100 ng/mL.
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What this article covers
- Overview
Definition: hemochromatosis is tissue injury from pathologic iron deposition, arising from hereditary hyperabsorption of dietary iron or secondarily from chronic transfusion therapy or ineffective erythropoiesis (as in beta-thalassemia).
- Epidemiology
Most common inherited cause: HFE-related hereditary hemochromatosis is the most common autosomal recessive genetic disorder in persons of northern European descent, with a carrier (heterozygote)…
- Risk factors
C282Y homozygosity: the dominant genetic risk, accounting for 80% to 90% of hereditary hemochromatosis with an identified HFE mutation.
- Pathophysiology
Hepcidin deficiency is central: HFE mutations impair the hepcidin response to rising iron stores, so hepcidin fails to suppress ferroportin, leaving duodenal enterocytes exporting iron into plasma regardless of body iron stores.
- Clinical features
Often asymptomatic at detection: most patients today are identified at an asymptomatic stage through abnormal iron studies found incidentally or on family screening, before organ damage occurs.
- Differential diagnosis
Secondary iron overload (transfusional or from ineffective erythropoiesis): elevated ferritin and transferrin saturation from repeated transfusions or hemolysis rather than HFE-driven…
- Diagnosis
Diagnosis is established by elevated fasting transferrin saturation and ferritin, then confirmed by HFE genetic testing: transferrin saturation above 45% with an elevated ferritin raises suspicion…
- Management
Confirm need for treatment first: asymptomatic heterozygous HFE carriers without elevated iron indices need no treatment or monitoring; treatment is reserved for C282Y homozygotes with biochemical or clinical evidence of overload.
- Complications
Cirrhosis and its sequelae: the dominant cause of morbidity, with portal hypertension, variceal bleeding, ascites, and hepatic encephalopathy once fibrosis is advanced.
- Prognosis
Normal life expectancy if treated early: patients without hepatic fibrosis or cardiomyopathy at diagnosis who undergo regular phlebotomy and monitoring have a normal life expectancy.
- Prevention
Screen first-degree relatives of every case: obtain fasting transferrin saturation, ferritin, and HFE genotyping regardless of symptoms.
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