From the Guidelines
The next step in the workup for Wilson disease after finding low ceruloplasmin is to measure 24-hour urinary copper excretion, as recommended by the Hepatology guidelines 1. This test should be performed by collecting all urine over a 24-hour period in a copper-free container.
- Normal urinary copper excretion is less than 40 mcg/24 hours,
- while patients with Wilson disease typically have values exceeding 100 mcg/24 hours,
- although values greater than 40 mcg/24 hours may indicate Wilson disease and require further investigation 1. Additionally,
- genetic testing for ATP7B mutations and
- slit-lamp examination for Kayser-Fleischer rings (copper deposits in the cornea) should be performed.
- Liver biopsy with quantitative copper measurement may also be necessary,
- with hepatic copper concentration greater than 250 mcg/g dry weight supporting the diagnosis. These tests are essential because low ceruloplasmin alone is not diagnostic,
- as it can occur in other conditions like malnutrition, protein-losing enteropathy, and severe liver disease 1. A comprehensive workup is important for accurate diagnosis since Wilson disease is treatable with copper chelation therapy (using agents like penicillamine, trientine, or zinc) but can lead to severe liver damage and neurological complications if left untreated.
From the FDA Drug Label
The diagnosis, if suspected on the basis of family or individual history or physical examination, can be confirmed if the plasma copper-protein ceruloplasmin** is less than 20 mg/dL and either a quantitative determination in a liver biopsy specimen shows an abnormally high concentration of copper (greater than 250 mcg/g dry weight) or Kayser-Fleischer rings are present The next step to workup Wilson's disease with low ceruloplasmin is to:
- Perform a quantitative determination in a liver biopsy specimen to check for an abnormally high concentration of copper (greater than 250 mcg/g dry weight)
- Check for the presence of Kayser-Fleischer rings 2
From the Research
Next Steps in Workup for Wilson Disease with Low Ceruloplasmin
- A low serum ceruloplasmin level is suggestive of Wilson disease, but it is not diagnostic on its own 3, 4
- The positive predictive value of a low serum ceruloplasmin level is low, ranging from 5.9% to 11.1% 3, 4
- Further testing is needed to confirm the diagnosis, including:
- 24-hour urinary copper excretion: a cutoff value of 0.64-1.6 μmol/24 hours has been suggested, with a sensitivity of 50.0-80.0% and a specificity of 75.6-98.3% 5, 6
- Hepatic copper content: a cutoff value of 4 μmol/g has been suggested, with a sensitivity of 65.7-94.4% and a specificity of 52.2-98.6% 5, 6
- Penicillamine challenge test: this test has been shown to be useful in the diagnosis of Wilson disease, with a significant increase in urinary copper excretion after penicillamine administration 7
- The Leipzig criteria, which include a combination of clinical and laboratory tests, can be used to help standardize the diagnosis and management of Wilson disease 5, 6
- It is essential to note that the diagnostic accuracy of these tests can vary depending on the population being tested, and the results should be interpreted with caution 5, 6