What are the typical laboratory findings in Wilson's disease, specifically regarding ceruloplasmin and serum free copper levels?

Typical Laboratory Findings in Wilson's Disease

In Wilson's disease, the typical laboratory findings are decreased ceruloplasmin and increased serum free copper (option C). 1

Pathophysiology and Laboratory Abnormalities

Wilson's disease is characterized by abnormal copper metabolism due to mutations in the ATP7B gene, resulting in copper accumulation in various tissues, particularly the liver and brain. The key laboratory findings include:

Ceruloplasmin

• Typically decreased in Wilson's disease (often <20 mg/dL or <200 mg/L)
• Usually markedly decreased in neurologic Wilson's disease
• May be in low-normal range in about half of patients with hepatic Wilson's disease 1
• Extremely low levels (<5 mg/dL or <50 mg/L) strongly suggest Wilson's disease 1

Serum Copper

• Total serum copper (which includes copper bound to ceruloplasmin) is usually decreased in proportion to decreased ceruloplasmin
• However, non-ceruloplasmin-bound copper (free copper) is typically elevated above 200 μg/L in untreated patients 1
• Free copper can be calculated by: Total serum copper (μg/L) - [3.15 × ceruloplasmin (mg/L)] 1, 2
• In most untreated patients, free copper is elevated above 25 μg/dL 1

Other Laboratory Findings

• 24-hour urinary copper excretion is typically elevated (>100 μg/24h or >1.6 μmol/24h) 1, 2
• Hepatic copper content is elevated (>4 μmol/g dry weight) 2

Clinical Correlation

The pattern of decreased ceruloplasmin with increased free copper is particularly important because:

1. It reflects the underlying pathophysiology - defective incorporation of copper into ceruloplasmin and impaired biliary copper excretion 3
2. The elevated free copper is the toxic form causing tissue damage 4
3. This pattern helps distinguish Wilson's disease from other conditions with low ceruloplasmin (such as malnutrition, protein-losing enteropathy, or aceruloplasminemia) 1

Important Caveats

• Serum ceruloplasmin alone is insufficient for diagnosis or exclusion of Wilson's disease 1

  • 15-36% of children with Wilson's disease may have normal ceruloplasmin levels 1
  • A prospective study showed subnormal ceruloplasmin had a positive predictive value of only 6% 1

• In acute liver failure due to Wilson's disease, total serum copper may be markedly elevated due to sudden release from liver tissue 1

• Non-ceruloplasmin-bound copper may also be elevated in:

  • Acute liver failure of any etiology
  • Chronic cholestasis
  • Copper intoxication 1

Diagnostic Algorithm

When suspecting Wilson's disease:

1. Measure serum ceruloplasmin (decreased in most cases)
2. Calculate non-ceruloplasmin-bound copper (typically elevated)
3. Measure 24-hour urinary copper excretion (typically elevated)
4. Look for Kayser-Fleischer rings by slit lamp examination
5. Consider liver biopsy for hepatic copper quantification if diagnosis remains uncertain
6. Genetic testing for ATP7B mutations for confirmation 2

The Leipzig scoring system can be used to establish the diagnosis, with a score ≥4 confirming Wilson's disease 1.