From the Guidelines
The diagnostic test for Wilson's disease is typically a combination of tests, including serum ceruloplasmin level, 24-hour urinary copper excretion, and hepatic copper content, as no single test is specific for the disease.
Diagnostic Tests
- Serum ceruloplasmin level: a low level (<0.1 g/L) is suggestive of Wilson's disease, but not always reliable as it can be low in other conditions such as autoimmune hepatitis, severe hepatic insufficiency, and celiac disease 1.
- 24-hour urinary copper excretion: a level >1.6 μmol/24 hr is typical in symptomatic patients, but may be only mildly elevated or normal in children with mild hepatic disease 1.
- Hepatic copper content: a level >4 μmol/g dry weight provides critical diagnostic information and should be obtained in cases where the diagnosis is not straightforward 1.
- Kayser-Fleischer rings: presence of these rings by slit-lamp examination is supportive of the diagnosis, but their absence does not exclude it, especially in patients with hepatic manifestation of the disease 1.
- Mutation analysis: specific testing for known mutations or haplotype analysis should be the primary mode for screening of first-degree relatives of patients with Wilson's disease 1.
Diagnostic Approach
A diagnostic score based on all available tests was proposed by the Working Party at the 8th International Meeting on Wilson’s disease, Leipzig 2001, which provides a good diagnostic accuracy 1. The approach to diagnosis of Wilson disease in a patient with unexplained liver disease or neurological disorder is outlined in figures 1 and 2 of the study by 1 and 1.
Important Considerations
It is essential to consider Wilson's disease in any individual with liver abnormalities or neurological movement disorders of uncertain cause, and not to exclude the diagnosis based on age alone 1. Additionally, the absence of Kayser-Fleischer rings or a normal serum ceruloplasmin level does not exclude the diagnosis, and further evaluation is necessary in such cases 1.
From the Research
Diagnostic Tests for Wilson's Disease
The diagnostic tests for Wilson's disease include:
- Serum free copper
- 24 hours urine copper estimation
- Hepatic copper estimation
- Genetic mutation testing
- Slit lamp eye examination for Kayser-Fleischer (KF) ring
- Serum ceruloplasmin level
Efficacy of Diagnostic Tests
The efficacy of different diagnostic tests for Wilson's disease has been studied, with results showing:
- Serum ceruloplasmin level has a sensitivity of 98.2% and specificity of 92.3% 2
- 24 hour urinary copper has a sensitivity of 100% and specificity of 63% 2
- KF ring has a sensitivity of 82.1% and specificity of 100% 2
- Combination of KF ring, serum ceruloplasmin, and basal 24 hour urinary copper excretion has a sensitivity of 70.4% and specificity of 100% 2
Limitations of Diagnostic Tests
The diagnostic tests for Wilson's disease have limitations, including:
- No single ideal diagnostic test that can exclude or confirm the disease with certainty 2
- Caeruloplasmin, 24-hour urinary copper, and hepatic copper content have variable sensitivity and specificity depending on the cut-off values used 3
- Genetic testing alone is not infallible and should not be used as the sole diagnostic test 4
Combination of Diagnostic Tests
A combination of diagnostic tests is recommended for the diagnosis of Wilson's disease, including: