Review Question - QID 214635

This boy who presents with personality changes, gait instability, and hemiballismus as well as Kayser-Fleischer rings in the iris most likely has Wilson disease, which is caused by a defect in biliary excretion of copper.

Wilson disease (also known as hepatolenticular degeneration) is caused by a mutation in the ATP7B transporter that is normally responsible for transcellular copper transport. A defect in this transport leads to failure of copper to enter circulation bound to ceruloplasmin as well as inadequate copper excretion into the biliary tree. Together, these mechanisms result in abnormal accumulation of copper in tissues such as the brain and liver where these ions create free radicals that damage surrounding cells. Patients can present earlier with psychiatric symptoms (e.g., hemiballismus), dementia, and Parkinson-like symptoms or later in life with cirrhosis. Labs will show decreased serum copper and decreased ceruloplasmin. A liver biopsy, if performed, would reveal increased hepatic copper. Treatment includes chelating agents such as penicillamine or trientine, though liver transplant may be required if patients are in the advanced stages of cirrhosis.

Figure/Illustration A shows an eye examination with a brown ring in the iris (between the red circles) that represents copper deposition. These "Kayser-Fleischer rings" are pathognomonic for Wilson disease.

Incorrect Answers:
Answer 2: Decreased glomerular excretion is responsible for uremia in patients with renal failure secondary to conditions such as glomerulonephritis or polycystic kidney disease. Uremia can present with confusion and fatigue but would not cause Kayser-Fleischer rings in the eyes.

Answer 3: Increased gastrointestinal absorption can be responsible for hypercalcemia in milk-alkali syndrome. Hypercalcemia can cause mental status changes but would also present with constipation, kidney stones, bone pain, and abdominal pain.

Answer 4: Increased pilosecretion of sodium chloride will be seen in patients with cystic fibrosis; however, this disease presents with pancreatic insufficiency, malabsorption, and respiratory infections.

Answer 5: Increased renal tubular absorption of organic acids can cause renal tubular acidosis. Acid-base imbalances can lead to mental status changes; however, they would not be associated with Kayser-Fleischer rings in the eye.

Bullet Summary:
Wilson disease is caused by a mutation in ATP7B that leads to decreased biliary excretion of copper and pathologic accumulation in hepatic and neural tissues.