Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study

Abstract

There is uncertainty regarding Wilson's disease (WD) management.

Objectives: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers.

Methods: Data on WD patients followed at 32 Spanish hospitals were collected.

Results: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response.

Conclusions: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.

Keywords: D-penicilamina; D-penicillamine; Diagnóstico genético; Enfermedad de Wilson; Gender; Genetic diagnosis; Género; Sales de zinc; Tetrathiomolibdate ammonium; Tetratiomolibdato de amonio; Trientina; Trientine; Wilson's disease; Zinc salts.