Author information
1School of Medicine, University of Minho, Braga, PRT.
2Paediatrics Department, Centro Materno-Infantil do Norte do Centro Hospitalar Universitário de Santo António, Porto, PRT.
3Internal Medicine Department, Centro Hospitalar de Vila Nova de Gaia / Espinho, Vila Nova de Gaia, PRT.
4Internal Medicine Department, Unidade Local de Saude do Alto Minho, Viana do Castelo, PRT.
5Paediatric Gastroenterology Department, Centro Hospitalar Universitário de São João, Porto, PRT.
6Paediatric Gastroenterology Department, Centro Materno-Infantil do Norte do Centro Hospitalar Universitario de Santo Antonio, Porto, PRT.
7Hepatology Unit of Internal Medicine Department, Centro Hospitalar de Tras-os-Montes e Alto Douro, Vila Real, PRT.
8Internal Medicine Department, Hospital Senhora da Oliveira Guimarães, Guimarães, PRT.
9Gastroenterology Department, Centro Hospitalar Universitário de São João, Porto, PRT.
10Life and Health Sciences Research Institute - ICVS/3B's Associated Laboratory and School of Medicine, University of Minho, Braga, PRT.
11Paediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital de Braga, Braga, PRT.
Abstract
Introduction Wilson's disease (WD) is a rare and underdiagnosed genetic disorder caused by anomalous tissue copper deposition, and for which epidemiological studies, specifically in Portugal, are scarce. Objectives This study aimed to evaluate the prevalence and incidence of WD and provide a description of its main clinical and laboratory features. Methods A retrospective study was carried out, with a search between 1995 and 2015, of all patients with a minimum follow-up of three months and birth confirmed in the northern region of Portugal, with an estimated population of 3,689,682 inhabitants. Database collection was based on the Portuguese National Health Service's clinical coding system, relying on clinical data from 13 northern Portuguese hospitals, liver biopsy histology results, and hospital prescription records. Clinical and biochemical correlations were statistically assessed using chi-square, Mann-Whitney U, Friedman, and Wilcoxon tests. Results Over the 20-year period, a prevalence of 1:37.000 and an incidence of one per million person-year was found. A total of 94 patients were analyzed, with a slight male predominance (53%), the majority with the onset of clinical manifestations in pediatric age (56%), with a median age at diagnosis of 16.6 years (interquartile range of 12.3-20,.8 years). Most patients presented with predominant liver disease (54.8%), with more than a third with cirrhosis; mixed hepatic and neurological manifestations in 17.9%; and mainly neurological symptoms in 10.7% of the patients. Neurological impairment was strongly associated with delayed development of the manifestations of the disease (p = 0.001) and also a higher detection of Kayser-Fleischer rings (p < 0.001), present in 27.0% of the patients. Regarding therapy, penicillamine has been the most widely used, with adverse reactions reported in 24.8%. At six and 12 months after initiation of therapy, a significant decrease in liver enzymes was found (ALT: p = 0.002; AST: p = 0.002, respectively), but no significant reduction was observed in urinary copper excretion. Conclusion This was one of the first studies regarding WD prevalence in a Portuguese population, contributing to a better understanding of the epidemiology, diagnosis, and management of WD in the northern region of Portugal. WD should be considered in any individual with unexplained hepatic or neurological manifestations, and initial symptoms may manifest at an early age, even in children less than five years old. A high percentage of patients were identified in the early stages of the disease by asymptomatic elevation of transaminases. Following copper chelation therapy, cytolysis markers appear to be more sensitive indicators of treatment response.