From the Guidelines
Wilson's disease should be considered in any individual with liver abnormalities or neurological movement disorders of uncertain cause, and a comprehensive diagnostic workup should be initiated to confirm the diagnosis. The symptoms of Wilson's disease can vary widely, but common presentations include liver problems such as jaundice, fatigue, abdominal pain, and elevated liver enzymes, as well as neurological symptoms like tremors, coordination problems, difficulty speaking, personality changes, and psychiatric disturbances 1. A key physical finding is the Kayser-Fleischer ring, a golden-brown ring around the cornea visible on eye examination.
Diagnostic Approach
The diagnostic workup for Wilson's disease typically begins with:
- Blood tests to evaluate serum ceruloplasmin levels, which are often low in patients with Wilson's disease, although normal levels do not exclude the diagnosis 1
- Measurement of 24-hour urinary copper excretion, which is typically elevated in symptomatic patients, with a basal level >1.6 μmol being suggestive of the disease 1
- Liver function tests, which are often abnormal
- Hepatic parenchymal copper content, which should be >4 μmol/g dry weight to support the diagnosis, especially in cases where the diagnosis is not straightforward or in younger patients 1
- Mutation analysis for specific allelic probes or whole-gene sequencing, which is useful for confirming the diagnosis and screening first-degree relatives of patients with Wilson's disease 1
Importance of Early Diagnosis
Early diagnosis of Wilson's disease is crucial because treatment with copper chelators like penicillamine, trientine, or zinc acetate can prevent disease progression and reverse many symptoms if started before permanent damage occurs 1. Brain MRI may also be useful in evaluating patients with neurological symptoms, as it can reveal characteristic changes in the basal ganglia.
Clinical Considerations
It's essential to consider Wilson's disease in the differential diagnosis of any patient with unexplained liver disease, especially when combined with neurological or neuropsychiatric disorders 1. The absence of Kayser-Fleischer rings does not exclude the diagnosis, and a low serum ceruloplasmin level should be taken as evidence for the diagnosis, with borderline levels requiring further evaluation 1.
From the FDA Drug Label
Wilson's disease (hepatolenticular degeneration) occurs in individuals who have inherited an autosomal-recessive defect that leads to an accumulation of copper far in excess of metabolic requirements The excess copper is deposited in several organs and tissues, and eventually produces pathological effects primarily in the liver, where damage progresses to postnecrotic cirrhosis, and in the brain, where degeneration is widespread Copper is also deposited as characteristic, asymptomatic, golden-brown Kayser-Fleischer rings in the corneas of all patients with cerebral symptomatology and some patients who are either asymptomatic or manifest only hepatic symptomatology Two types of patients require treatment for Wilson's disease: (1) the symptomatic, and (2) the asymptomatic in whom it can be assumed the disease will develop in the future if the patient is not treated 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 symptoms of Wilson's disease include:
- Hepatic symptoms
- Neurologic symptoms, such as:
- Ataxia
- Tremors
- Speech difficulties
- Psychiatric manifestations, such as:
- Irritability
- Depression
- Deterioration of work performance
- Kayser-Fleischer rings in the corneas
The workup for Wilson's disease includes:
- Plasma copper-protein ceruloplasmin level
- Quantitative determination of copper in a liver biopsy specimen
- Presence of Kayser-Fleischer rings 2
From the Research
Symptoms of Wilson's Disease
- Depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser-Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, and arthralgia 3
- Coombs-negative hemolytic anemia is a key feature of Wilson disease with undetectable serum haptoglobin 3
- Liver disease, neurological disease of the movement disorder type, or a wide array of behavioural disturbances 4
- Hepatic, neurological, psychiatric, ophthalmological, and other derangements 5
Workup of Wilson's Disease
- Modified Leipzig Scoring System helps diagnose Wilson disease 3
- Urine copper, blood ceruloplasmin, slit lamp examination for Kayser-Fleischer rings, and liver biopsy with quantitative copper assay 4
- Genetic testing is impractical because of the multitude of mutations that have been identified, so accurate diagnosis relies on judicious use of a battery of laboratory and other diagnostic tests 5
- Diagnosis can be made if two of the following symptoms are present: Kayser-Fleischer rings; topical neurologic symptoms; and low serum ceruloplasmin levels 6
- In less typical cases diagnosis requires various other tests of copper metabolism 6