Hemochromatosis

Pathophysiology

1) systemic tissue damage caused by excess iron 2) occurs in primary form (due to increased iron absorption with deposition in parenchymal cells) and secondary form (due to chronic blood transfusions or hemoglobinopathies like thalassemia and the porphyrias) 3) causes damage to heart, liver, pancreas, pituitary, and joints

Signs and Symptoms

1) classic triad of micronodular cirrhosis, diabetes, skin discoloration – “bronze diabetes 2) splenomegaly 3) hepatic encephalopathy (owing to cirrhosis) 4) striking venous pattern on torso 5) arthritis that usually affects fingers first (25-50%)

Characteristic Test Findings

Laboratory – 1) greatly increased serum ferritin 2) increased transferrin saturation 3) renal excretion of iron is limited to 1 mg/day

Histology/Gross Pathology

1) hemosiderin buildup in liver, pancreas, heart, spleen, and bone marrow 2) deposition of calcium pyrophosphate dihydrate (CPPD) crystals in joints

Associated Conditions

1) restrictive cardiomyopathy with subsequent congestive heart failure 2) esophageal varices 3) increased risk of hepatocellular carcinoma (30%) 4) HLA a3 (70%)

Inheritance/Epidemiology

1) autosomal recessive 2) male to female, 5:1, 3) presents at 40-60 years of age 4) more common in northern European ancestry 5) HFE gene defect on chromosome 6P

Treatment

1) strict dietary limits on iron intake 2) regular phlebotomy 3) deferoxamine

Tips for USMLE

1) if a middle-aged man presents to the ER coughing up blood and has bronzed skin, an enlarged liver, and hyperglycemia, think hemochromatosis