Wilson’s disease is a rare, inherited condition that causes the body to retain too much copper, a metal that is toxic in excess. This disorder (ICD-10 code E83.0) results from a defect in the copper transport system, leading to accumulation primarily in the liver and brain. Since the disease is treatable, an accurate and timely diagnosis is absolutely necessary to prevent life-threatening organ damage and irreversible neurological complications. The diagnostic process is complex, requiring clinical observation, specialized laboratory tests, and imaging.
Initial Clinical Suspicion
Diagnosis begins when a physician recognizes vague symptoms suggesting copper toxicity. Wilson’s disease can present in three main ways: liver disease, neurological dysfunction, or psychiatric illness, which makes initial identification challenging.
Hepatic presentation often occurs in adolescents, ranging from unexplained chronic hepatitis or liver enzyme elevation to acute liver failure. Neurological symptoms, common in young adults, include tremors, difficulty speaking (dysarthria), and coordination problems, often mimicking Parkinson’s disease.
Psychiatric manifestations are frequent, including significant changes in personality, depression, and emotional lability. A specialized eye exam is highly informative. An ophthalmologist uses a slit lamp to look for Kayser-Fleischer (KF) rings—greenish-brown deposits of copper in the cornea. While these rings are not present in all patients (especially children with only liver disease), their presence is highly suggestive of Wilson’s disease, particularly when neurological symptoms are evident.
Biochemical Markers in Blood and Urine
Specialized laboratory tests measure indicators of copper metabolism once clinical suspicion is raised. A standard initial test measures serum ceruloplasmin, the protein responsible for carrying most copper in the bloodstream.
In most patients, ceruloplasmin levels are abnormally low, typically less than \(0.2 \text{ g/L}\). However, inflammation from severe liver disease can falsely elevate this acute phase reactant into the low-normal range, making the test inconclusive in 10 to 20% of cases.
Measurement of total serum copper is also standard, but it is often low or normal despite copper overload. This occurs because the decrease in copper-carrying ceruloplasmin pulls the total serum copper level down, even though the toxic, unbound copper fraction is dangerously high.
The 24-hour urinary copper excretion test is a more reliable non-invasive indicator. This test measures the amount of copper excreted over a full day. In symptomatic patients, this measurement is typically elevated, often exceeding \(1.6 \text{ \mu mol/24h}\) (or \(100 \text{ \mu g/24h}\)), suggesting a defect in copper excretion.
Confirmatory Tissue and Imaging Analysis
Confirmatory tests are necessary when initial biochemical results are inconclusive or when specific organ damage needs to be assessed. The quantitative measurement of copper concentration in liver tissue via biopsy is widely regarded as the gold standard for diagnosis.
A concentration greater than \(250 \text{ \mu g}\) of copper per gram of dry liver tissue is diagnostic of Wilson’s disease, even in asymptomatic patients. This procedure is helpful when ceruloplasmin levels are normal or near-normal due to inflammation.
Imaging analysis, primarily Magnetic Resonance Imaging (MRI), is crucial, especially for patients with neurological symptoms. Brain MRI identifies characteristic lesions caused by copper toxicity, which appear as bright areas on T2-weighted and FLAIR sequences.
These changes are often found symmetrically in the basal ganglia (putamen and caudate nucleus), the thalamus, and the brainstem. While common in neurological Wilson’s disease, these brain changes can also indicate copper deposition in those with hepatic presentation or in asymptomatic individuals.
Genetic Testing and Family Screening
Genetic testing provides a highly specific method of confirming the diagnosis by looking for mutations in the \(ATP7B\) gene. This gene, located on chromosome 13, contains the instructions for a protein that transports excess copper out of liver cells into the bile for excretion. The identification of two pathogenic mutations (one from each parent) in the \(ATP7B\) gene confirms the diagnosis of Wilson’s disease, which is inherited in an autosomal recessive pattern.
Over 700 different mutations in the \(ATP7B\) gene have been identified, making genetic sequencing complex. A negative genetic test does not completely rule out the disease because a rare or undiscovered mutation may be present. Therefore, a combination of clinical and biochemical data is still necessary for a full diagnosis. Once a person is diagnosed, genetic testing becomes necessary for family screening, particularly for first-degree relatives. This screening allows for the early identification of asymptomatic relatives who carry two faulty genes, enabling immediate treatment to prevent the onset of irreversible organ damage.