Unusually high absorption of iron (4 mg/day; normal = 1 mg/day). - Age ~50 years (slighly later in women)

Types:- Primary (hereditary) hemochromatosis: Genemutation in HFE on chromosome 6 → C282Y or H63D mutation. Associated with HLA-A3- HFE mutation → defective binding of transferrin to its receptor → liver stops producing hepcidin → unregulated ferroportin causes ↑ iron reabsorption in duodenal enterocytes- Secondary hemochromatosis: Frequent blood transfusions, hemolytic diseases, porphyria cutanea tarda

Iron can cause free radicals using the Fenton reaction → cellular damage → cell death → tissue fibrosis.

Clinical features:- Asymptomatic in 75% of cases- Abdominal pain, hepatomegaly → liver cirrhosis (+ hepatocellular carcinoma)- Fatigue, lethargy- Hyperpigmented, bronze skin - Signs of diabetes mellitus (polydipsia, polyuria)- Arthralgia, chondrocalcinosis- Erectile dysfunction, testicular atrophy, loss of libido, amenorrhea- Cardiomyopathy (restrictive or dilated) → congestive heart failure, arrhythmias - Type I diabetes melitus (destruction of islet cells) or malabsorption (destruction of exocrine pancreas)

Diagnosis:- ↑ iron, ↑ transferrin saturation (normal: 15-45%), total iron binding capacity ↓, ↑ ferritin- Liver biopsy: Brown spots (DD: Lipofuscin) → Confirm with Prussian blue stain

Treatment: Phlebotomy, deferoxamine