From the Guidelines
Wilson's disease diagnosis should be considered in any individual with liver abnormalities or neurological movement disorders of uncertain cause, and a combination of clinical evaluation, laboratory tests, and genetic analysis should be used to confirm the diagnosis. When evaluating a patient for Wilson's disease, the following tests should be considered:
- Serum ceruloplasmin level, which should be taken as evidence for the diagnosis if low, but borderline levels require further evaluation 1
- Slit-lamp examination for Kayser-Fleischer rings, which should be sought by a skilled examiner, but the absence of Kayser-Fleischer rings does not exclude the diagnosis 1
- Basal 24-hour urinary excretion of copper, which is typically elevated in symptomatic patients, but may be only mildly elevated or even in the normal range in children with mild hepatic disease 1
- Hepatic parenchymal copper content, which provides critical diagnostic information and should be obtained in cases where the diagnosis is not straightforward and in younger patients 1
- Mutation analysis with specific allelic probes or by whole-gene sequencing, which is currently possible and available, and should be the primary mode for screening of first-degree relatives of patients with Wilson’s disease 1 It is also important to consider neurologic evaluation and imaging of the brain, preferably by MR imaging, in all patients with neurologic Wilson’s disease and should be part of the evaluation of any patient presenting with neurological symptoms consistent with Wilson’s disease 1. A liver biopsy with quantitative copper measurement can also provide definitive evidence of the diagnosis, and genetic testing for mutations in the ATP7B gene can confirm the diagnosis 1. Early diagnosis is crucial as treatment with copper chelators or zinc salts can prevent progression of liver disease and neurological symptoms, and family screening is recommended for first-degree relatives of affected individuals since Wilson's disease has an autosomal recessive inheritance pattern.
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 diagnosis of Wilson's disease can be confirmed by:
- Low plasma copper-protein ceruloplasmin levels (less than 20 mg/dL)
- High concentration of copper in a liver biopsy specimen (greater than 250 mcg/g dry weight)
- Presence of Kayser-Fleischer rings 2
From the Research
Diagnostic Criteria for Wilson's Disease
The diagnosis of Wilson's disease is based on a combination of clinical features, biochemical tests, and molecular analysis 3. The key diagnostic criteria include:
- Clinical features such as liver or brain injury due to accumulation of copper
- Biochemical tests including plasma ceruloplasmin concentration, 24h urinary copper excretion, and copper content in the liver
- Molecular analysis to identify mutations in the Wilson's disease gene
Biochemical Tests for Wilson's Disease
Biochemical tests play a crucial role in the diagnosis of Wilson's disease. These tests include:
- Serum ceruloplasmin concentration: decreased levels are indicative of Wilson's disease 4
- Urinary copper content: increased levels are indicative of Wilson's disease 4
- Hepatic copper concentration: elevated levels are indicative of Wilson's disease 4
- Serum non-caeruloplasmin-bound ('free') copper: elevated levels are indicative of Wilson's disease 5
Importance of Early Diagnosis and Treatment
Early diagnosis and treatment of Wilson's disease are critical to prevent long-term complications and improve quality of life 3, 6. Delayed diagnosis and treatment can lead to worse outcomes, particularly in patients with neurological and psychiatric symptoms. Regular monitoring of treatment response and adherence to therapy are essential to ensure optimal outcomes.
Diagnostic Challenges
The diagnosis of Wilson's disease can be challenging due to the diverse patterns of presentation and the lack of a single reliable diagnostic feature 7. A high index of suspicion and a comprehensive diagnostic approach are necessary to establish a diagnosis of Wilson's disease. Consideration of Wilson's disease should be given to patients of any age with obscure hepatic or neurological abnormalities 7.