Challenges and dilemmas in pediatric hepatic Wilson’s disease

Table 1 Various laboratory investigations used in the diagnosis and monitoring of Wilson disease

Diagnostic tests	Cut-off values in diagnosis	Disease monitoring	Problems in interpretation
Serum ceruloplasmin	< 10 mg/dL (strong evidence), 10-20 mg/dL (needs further evaluation), 20-40 mg/dL (normal value, but does not exclude diagnosis)	Not helpful	Can be normal in fulminant presentation and acute inflammation as it is an acute phase reactant
24-h urine copper	> 100 mcg/d (virtually diagnostic in symptomatic patients), > 40 mcg/d (may indicate disease, needs further evaluation)	> 500 mcg/d during initial phase, 200-500 mcg/d in the maintenance phase	Difficult to perform, to be done in reliable laboratories
Hepatic copper	> 250 mcg/g dry weight (diagnostic), 50-250 mcg/g dry weight (needs further evaluation), < 50 mcg/g dry weight (normal)	Not recommended	Inhomogenous distribution of copper (sampling error), elevated in long-standing cholestasis
Serum total copper	> 25 micromol/L (needs further evaluation), 14-24 micromol/L (90-150 mg/dL) normal	N/Aa
Non-ceruloplasmin copper	10-15 mcg/dL (normal person), > 25 μg/dL (untreated patients), Not recommended for diagnosis	> 15 mg/dL (poor compliance)a < 5 mg/dL (over-chelation)
Exchangeable copper	> 2.08 micromol/L (more likelihood of extrahepatic organ involvement), 0.62 and 1.15 micromol/L (normal)	Experimental	Requires equipped laboratories and expertise
Relative exchangeable copper	> 15% (100% sensitivity and specificity for diagnosis)	Experimental	Requires equipped laboratories and expertise

^aThe serum free copper or NCC has a role in monitoring: Initial phase: > 25 mcg/dL, maintenance phase: 10-15 mcg/dL, under-chelation: > 15 mcg/dL, over-chelation: < 5 mcg/dL.