A 36-year-old male presents because his skin has been darkening recently. You notice that his skin has a dark, somewhat bronze color. Workup reveals signs of diabetes mellitus. His serum iron is found to be 1150 mg/dL, and his transferrin saturation is 98%. A liver biopsy is performed and reveals extensive deposits of hemosiderin in the hepatocytes and Kupffer cells. The mechanism most likely responsible for this constellation of findings is
Abnormalities of metabolism are associated with a diverse group of liver diseases. Hemochromatosis (excessive accumulation of body iron) may be primary or secondary. Primary hemochromatosis is a genetic disorder of iron metabolism that is inherited as an autosomal recessive disorder. The classic clinical triad for this disease consists of micronodular pigment cirrhosis, diabetes mellitus, and skin pigmentation. The combination of diabetes and skin pigmentation is called bronze diabetes. In the majority of patients serum iron is above 250 mg/dL, serum ferritin is above 500 ng/dL, and iron (transferrin) saturation approaches 100%. In patients with primary hemochromatosis, the excess iron is deposited in the cytoplasm of parenchymal cells of many organs, including the liver and pancreas. Liver deposition of iron leads to cirrhosis, which in turn increases the risk of hepatocellular carcinoma. Iron deposition in the islets of the pancreas leads to diabetes mellitus. Iron deposition in the hea leads to congestive hea failure, which is the major cause of death in these patients. Deposition of iron in the joints leads to ahritis, while deposition in the testes leads to atrophy. Secondary hemochromatosis, also called systemic hemosiderosis, is most common in patients with hemolytic anemias, such as thalassemia. Excess iron may also be due to an excessive number of transfusions or to increased absorption of dietary iron. In idiopathic (primary) hemochromatosis, iron accumulates in the cytoplasm of parenchymal cells, but in secondary hemochromatosis the iron is deposited in the mononuclear phagocytic system. In both conditions the iron is deposited as hemosiderin, which stains an intense blue color with Prussian blue stain. Since the iron deposition does not usually occur in the parenchymal cells in secondary hemochromatosis, there usually is no organ dysfunction or injury Reference: Robbins & Cotran Pathologic Basis of Disease, 9edition
Defective excretion of copper into the bile
Defective synthesis of a1 antitrypsin
Excessive reabsorption of iron from the small intestines
Excessive absorption of galactose from the small intestines
miscellaneous