Question

Consider the following conditions: 1. Copper absorption is high. 2. Urinary excretion of copper is high. 3. Ceruloplasmin is high. 4. Tissue deposition is high. Which of these are true in the case of Wilson's disease?

• A. 1, 2 and 3
• B. 3 and 4
• C. 1, 2 and 4
• D. 1, 2, 3 and 4

Hint:

Think about what happens to copper when the liver cannot load it onto its carrier protein.

Answer 1

The Correct Option is C

Step 1: Understanding the Question:
This question tests the biochemical profile of Wilson's disease, an autosomal recessive disorder of copper metabolism. It asks which of four proposed changes in copper handling actually occur in this condition.

Step 2: Key Concept or Approach:
Wilson's disease results from a mutation in the ATP7B gene, which codes for a copper-transporting ATPase in the liver. This defect blocks two normal processes: incorporation of copper into ceruloplasmin, and biliary excretion of excess copper. Ingested copper is still absorbed normally or even excessively from the gut, but it cannot be packaged into ceruloplasmin or cleared through bile, so it accumulates in the liver, brain, cornea, and kidneys, and spills over into the urine.

Step 3: Working Through the Options:
Statement 1, that copper absorption is high, is true, since intestinal copper uptake is preserved or increased. Statement 2, that urinary excretion of copper is high, is true, because copper that cannot be excreted via bile circulates as free copper and is filtered into urine, which is why 24-hour urinary copper is used as a diagnostic test. Statement 3, that ceruloplasmin is high, is false, and is the classic trap in this question: ceruloplasmin is actually low in most patients with Wilson's disease, because the ATP7B defect prevents copper from being loaded onto apoceruloplasmin, so the unstable apo-form is degraded rapidly. Statement 4, that tissue deposition is high, is true, since copper builds up in the liver, causing hepatitis and cirrhosis, in the basal ganglia, causing tremor and dystonia, and in the cornea, producing the Kayser-Fleischer ring.

Step 4: Conclusion:
The true statements in Wilson's disease are increased copper absorption, increased urinary copper excretion, and increased tissue deposition, so "1, 2 and 4" is correct, while ceruloplasmin is actually low rather than high.