Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre

Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging.

We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or 3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value<0.05) associated with the chi-squared test in contingency tables. Multivariate analysis was performed by logistic regression using SPSS 10.

There were 31 males (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97 years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29 patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The classic diagnosis was made in 32 patients (58.18%). In the univariate analysis the non-classic diagnosis was associated with: age>18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors.

In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.