A 45-year-old man comes to the office for progressive weakness and fatigue over the last year. The patient was adopted and does not know his family history. After a comprehensive physical examination and laboratory evaluation, the patient undergoes genetic testing. A loss of expression mutation is identified in a gene coding for a protein found on the basolateral surface of hepatocytes and enterocytes. The protein is known to interact with the transferrin receptor. Which of the following conditions is this patient at greatest risk of developing?

Question

A 45-year-old man comes to the office for progressive weakness and fatigue over the last year.  The patient was adopted and does not know his family history.  After a comprehensive physical examination and laboratory evaluation, the patient undergoes genetic testing.  A loss of expression mutation is identified in a gene coding for a protein found on the basolateral surface of hepatocytes and enterocytes.  The protein is known to interact with the transferrin receptor.  Which of the following conditions is this patient at greatest risk of developing?

Quizplus · Accepted Answer

11ec160b_3979_6114_9249_eb5042c78035_MD0001_00 Primary hemochromatosis (ie, hereditary hemochromatosis) is most commonly caused by mutations affecting the HFE protein. This protein normally interacts with the transferrin receptor to form a complex that functions as a sensor of iron stores. Mutations that inactivate the HFE protein cause enterocytes and hepatocytes to detect falsely low iron levels. This increases iron accumulation in the body through the following 2 mechanisms: When body iron levels exceed 20 g, patients typically develop the classic triad of micronodular cirrhosis, diabetes mellitus, and skin pigmentation (ie, "bronze diabetes"). These patients are at an increased risk for hepatocellular carcinoma, congestive heart failure, and testicular atrophy/hypogonadism. (Choice A) Basal ganglia atrophy is a potential complication commonly seen in Wilson disease (ie, hepatolenticular degeneration). (Choice B) Exocrine pancreatic function is usually preserved in patients with hemochromatosis. Therefore, fat malabsorption and osteoporosis (due to decreased vitamin D) would not typically be seen. (Choice C) Iron deficiency anemia is a potential complication of blood loss, lack of dietary iron, or an inability to absorb iron (eg, celiac disease). Hemochromatosis results in iron overload, not iron deficiency. (Choice E) Pulmonary emphysema is a potential complication of alpha-1 antitrypsin deficiency. Educational objective: HFE protein mutations are the most common cause of primary hemochromatosis. Inactivation of the HFE protein results in decreased hepcidin synthesis by hepatocytes and increased DMT1 expression by enterocytes, leading to iron overload. Patients with hemochromatosis are at an increased risk for liver cirrhosis and hepatocellular carcinoma. __________ References: Hepcidin regulation of iron transport. (http://www.ncbi.nlm.nih.gov/pubmed/18936232)

A 45-Year-Old Man Comes to the Office for Progressive Weakness