Review Question - QID 104793

This patient with jaundice, a Kayser-Fleischer ring, central nervous system dysfunction, and changes in behavior has a presentation consistent with Wilson disease. This condition is associated with high 24-hour urinary copper excretion.

Wilson disease, also known as hepatolenticular degeneration, is a rare autosomal recessive disorder linked to chromosome 13, in which there is a defect in copper transport, impaired biliary excretion of copper, and excessive copper deposition in the liver and brain. Multiple organ systems are affected including the liver (often leading to cirrhosis), the basal ganglia (extrapyramidal symptoms, neuropsychiatric changes, and dementia), and joints (degenerative arthritis). Laboratory values are notable for an elevated 24-hour urinary copper excretion and a decreased serum ceruloplasmin level (which, in turn, leads to a correspondingly low total serum copper level). Management typically includes the administration of copper chelating agents such as D-penicillamine, oral zinc supplementation, as well as supportive care for cirrhosis that develops as a result of the disease. Some patients will present in acute liver failure, and liver transplantation is often required for these patients or those with advanced liver disease unresponsive to medical management.

Mulligan et. al review Wilson disease. They describe the pathophysiology of impaired copper metabolism and the development of advanced liver disease. They discuss options for management including the use of various chelating agents as well as indications for liver transplant.

Figure A shows a Kayser-Fleischer ring, depicted by the brownish copper deposit on the inside surface of the peripheral cornea. Considered pathognomonic for Wilson disease, Kayser-Fleischer rings can also rarely be seen in patients with prolonged cholestasis or cryptogenic cirrhosis.

Incorrect Answers:
Answer 2: Elevated blood lead level would represent lead toxicity. While neurologic symptoms are common, jaundice would not be expected. Abdominal pain, a microcytic anemia, and cognitive changes can be seen.

Answer 3: Elevated serum ceruloplasmin would not be typical. Patients with Wilson disease characteristically have low serum ceruloplasmin levels due to deranged copper metabolism.

Answer 4: Elevated serum copper levels would not be expected. Total serum copper levels are expected to be decreased in Wilson disease given the decreased levels of serum ceruloplasmin which is the main protein carrier of copper.

Answer 5: Elevated serum ferritin is associated with hemochromatosis. While hemochromatosis may also result in end stage liver disease, a history of bronzed skin, diabetes, and arthritis would be expected.

Bullet Summary:
Wilson disease presents with jaundice as well as neurologic dysfunction, and is characterized by an elevated 24 hour urinary copper excretion.