From the Guidelines
Wilson's disease diagnosis should be based on a combination of clinical symptoms, laboratory tests, and genetic analysis, including serum ceruloplasmin, 24-hour urinary copper excretion, and mutation analysis of the ATP7B gene, as recommended by the EASL clinical practice guidelines 1. When evaluating a patient for Wilson's disease, the following laboratory tests should be considered:
- Serum ceruloplasmin level, with levels below 20 mg/dL suggestive of Wilson's disease 1
- 24-hour urinary copper excretion, with levels exceeding 1.6 μmol (100 μg) strongly supporting the diagnosis 1
- Slit-lamp examination for Kayser-Fleischer rings, although their absence does not exclude the diagnosis 1
- Genetic testing for mutations in the ATP7B gene, which can confirm the diagnosis, particularly in ambiguous cases or for family screening 1
- Liver function tests to assess hepatic involvement, and a liver biopsy with quantitative copper measurement may be necessary in unclear cases 1
- MRI of the brain to identify neurological involvement 1 It is essential to note that no single test can diagnose Wilson's disease, and a combination of these tests is necessary to confirm the diagnosis. A low serum ceruloplasmin level, high 24-hour urinary copper excretion, and presence of Kayser-Fleischer rings are indicative of Wilson's disease, but genetic testing is necessary to confirm the diagnosis 1.
From the Research
Wilson's Disease Lab Testing
- Wilson's disease is an autosomal recessive disorder of copper metabolism, and diagnosis relies on a combination of clinical suspicion, typical neurological symptoms, presence of Kayser-Fleischer rings, and reduced serum ceruloplasmin concentration 2.
- The conventional value of < 0.20 g/l for serum ceruloplasmin is not a universal diagnostic value, and age of the subjects and analytical variations should be considered when interpreting these levels 2.
- Patients with inconclusive findings require further investigations such as:
- 24 h urinary free-copper excretion
- Penicillamine challenge test
- Liver copper measurement
- Detection of gene mutations
- Direct molecular diagnosis remains the most decisive tool for diagnosing Wilson's disease 2.
- Serum ceruloplasmin level is considered a diagnostic test for Wilson's disease, but the positive predictive value of low serum ceruloplasmin is only 5.9% 3.
- Laboratory diagnosis of Wilson's disease is confirmed by:
- Decreased serum ceruloplasmin
- Increased urinary copper content
- Elevated hepatic copper concentration 4.
- Measuring serum caeruloplasmin non-immunologically is important for diagnosing Wilson's disease, and the first diagnostic screening test is the estimation of the serum caeruloplasmin and total serum copper concentrations, with calculation of the serum non-caeruloplasmin-bound ('free') copper 5.
- Diagnosis may be confirmed by an elevated urinary copper excretion, and all close relatives of an identified patient must be screened 5.