MEDizzy - A 36-year-old man presents because his skin has been

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Gastrointestinal System

A 36-year-old man presents because his skin has been darkening recently. Physical examination finds his skin to have 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. Which one of the listed genes is mutated in the familial form of this man’s disease?

ExplanationSeveral quite different liver diseases result from abnormalities of metabolism. Hemochromatosis results from excessive accumulation of body iron. The disease may be primary or secondary. Primary (familial) hemochromatosis is a genetic disorder of iron metabolism that is inherited as an autosomal recessive disease. Excess iron is absorbed from the small intestines because of a mutation of the HFE gene, the product of which normally controls the small intestinal absorption of iron. 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 heart leads to congestive heart failure, which is the major cause of death in these patients. Deposition of iron in the joints leads to arthritis, while deposition in the testes leads to atrophy.