In cases where a final diagnosis cannot be reached based on clinical signs and symptoms and non-invasive tests, or if additional liver pathologies are suspected, liver biopsy may be required to quantify hepatic copper concentration and assess liver histology.2-4 Liver histology alone is not sufficient for Wilson disease diagnosis as the main features are non-specific and can overlap with other disorders, resulting in misdiagnosis.4 Copper staining methods often used on liver biopsies, such as rhodanine, produce highly variable results and can fail to identify increased liver copper content.4,17
Current diagnostic guidelines also recommend the use of brain imaging, including MRI, as over 90% of patients with Wilson disease with neurologic symptoms have brain pathologies detectable by MRI.2,3,18,19 A validated method for quantifying pathologies on brain MRI in Wilson disease was lacking until a novel, semi-quantitative, MRI visual rating scale was developed and validated for the assessment and classification of radiologic severity in Wilson disease.20 This semi-quantitative MRI rating scale may be useful for patient monitoring during therapy.20
Establishing a diagnosis of Wilson disease can require consideration of the results of multiple diagnostic investigations, and the Leipzig diagnostic scoring system was developed to aid this process.2 This system uses the results of common diagnostic tests and symptoms to provide a score indicating the likelihood of a patient having Wilson disease and whether further tests are required to confirm the diagnosis.21
Between 18% and 23% of patients with Wilson disease remain presymptomatic with only mild elevations in liver tests.12 It is, therefore, important that a thorough examination of patients is carried out so that subtle or mild manifestations are detected at an early stage.2,3,12