Snapshot A 42-year-old woman with a history of polycystic ovarian syndrome and diabetes presents to her primary care physician's office for abdominal pain. She reports that she has experienced this for the past few months. On physical exam, her skin is noted to be hyperpigmented. She also has hepatomegaly. Given these findings, her physician sends her for laboratory testing, which shows elevated transaminases, iron, and ferritin. She is scheduled for regular phlebotomy. Introduction Clinical definition hemochromatosis is a disease of iron accumulation, characterized by the classic triad cirrhosis diabetes mellitus skin pigmentation Epidemiology demographics age > 40 detected in men earlier than women women lose iron through menstruation etiology hereditary hemochromatosis secondary causes repeated blood transfusions Pathogenesis ↑ intestinal absorption of iron, leading to iron overload iron accumulation in organs cause end-organ damage Genetics autosomal recessive HFE gene mutation on chromosome 6 C282Y mutation H63D mutation associated with HLA-A3 Presentation Symptoms cirrhosis abdominal pain hepatomegaly jaundice spider angioma palmar erythema diabetes mellitus hyperpigmentation of skin found in late-stage disease "bronze diabetes" arthropathy calcium pyrophosphate deposition in metacarpophalangeal joints hypogonadism gynecomastia lack of body hair systemic symptoms weakness fatigue heart failure Studies Diagnostic testing imaging magnetic resonance imaging (MRI) of the liver to evaluate iron load studies liver biopsy Prussian blue stain detects iron deposition in hepatocytes ↑ liver enzymes iron studies ↑ transferrin saturation > 45% ↑ ferritin ↑ iron ↓ TIBC genetic testing for HFE mutation confirms the diagnosis Diagnostic criteria based on clinical history and exam with ↑ transferrin saturation or ferritin Nonalcoholic fatty liver disease (NAFLD) distinguishing factor increased ferritin levels are also found in NAFLD, but transferrin saturation levels are normal and imaging will not show increased iron deposition in the liver Vibrio vulnificus infection distinguishing factors associated with hemochromatosis and bullous skin lesions associated with exposure to seafood Treatment First-line regular phlebotomy indication to maintain ferritin levels 50-100 mcg/L iron chelation therapy deferasirox deferoxamine deferiprone Second-line liver transplant indication decompensated cirrhosis Complications Hepatocellular carcinoma patients should undergo regular screening Cardiomyopathy dilated > restrictive