Gender differences in Wilson's disease

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Abstract

Background

Wilson's disease (WD) is an inherited disorder of copper metabolism. Although well documented in many disorders, gender hasn't been directly addressed in WD; therefore, our aim was to evaluate gender differences in WD.

Methods

We analyzed data on 627 consecutive WD patients entered into our registry (1958–2010).

Results

We observed a male predominance in our population of WD patients (327 males vs. 290 females; p < 0.05). At disease diagnosis, 510/627 patients were symptomatic, most patients had the neuropsychiatric WD form (345/510; p < 0.01). The neuropsychiatric form occurred predominantly in men versus women (209/278 vs. 136/232; p < 0.01), especially the rigidity-tremor (71/111 vs. 40/111; p < 0.05), rigidity (23/33 vs. 10/33; p = 0.07) and psychiatric forms (46/71 vs. 25/71; p = 0.06). The hepatic form occurred more frequently in women (96/165 vs. 69/165; p < 0.01) and women developed the neuropsychiatric form 2 years later than men (29.4 vs. 27.1; p < 0.05).

Conclusions

According to our findings, the neuropsychiatric form of WD is predominant at diagnosis in both genders. The hepatic form of WD occurs more frequently in women, and women develop the neuropsychiatric form of disease almost 2 years later than men. We speculate these differences may be due to the protective effect of estrogens and iron metabolism differences.

Introduction

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism (OMIM 277900), which results in the impairment of copper incorporation into ceruloplasmin. This disturbance is caused by impairment of the copper transporting ATP-ase, ATP7B, which produces abnormal copper accumulation in many tissues (liver, cornea, brain, kidney, and heart) with secondary damage of affected organs [1]. WD is a rare disorder and there are no large epidemiologic studies evaluating it. Especially, there are only short notes about gender-related phenotypic differences in WD [2], [3], [4], [5], [6], [7]. Gender differences have been recently found to occur in many human pathological conditions, including liver and neurodegenerative disease. It is hypothesized that these differences are related to the impact of sex-hormones and/or gender-related differences in iron metabolism [8], [9], [10], [11], [12], [13], [14], [15]. Gender-dependent differences are very well documented in Parkinson's disease, where estrogen may protect dopaminergic neurons and affect the metabolism of dopamine. In some hepatic and neurological disorders, gender differences in iron metabolism may play an important role [13], [14], [15]. It is thought, for example, that the higher iron level in the liver of men could be predictive of liver fibrosis in chronic hepatitis [13], and the lower ferritin iron level in the brains of women may protect them against neurodegenerative disorders [15], [16]. Similar mechanisms could also play an important role in WD. Here, we analyzed the influence of gender on WD.

Section snippets

Patients and methods

We studied 627 patients with WD who were previously examined and had a confirmed diagnosis from the Institute of Psychiatry and Neurology in Warsaw (Poland) between 1958 and 2010. The study was approved by local ethics committee. The patients' diagnoses were based on clinical symptoms, abnormal copper metabolism (decreased level of serum ceruloplasmin and serum copper, and increased 24 h urine copper excretion), presence of the Kayser–Fleischer (K–F) ring, and in many cases also with genetic

Statistical analysis

All data were analyzed using Statistica v.9. The mean, range, percentage, and standard deviation (SD) were noted for descriptive summary statistics. Quantitative variables were compared using the Mann–Whitney U test. Categorical variables were compared between groups by the chi-square test and Fisher's test; p < 0.05 was considered significant and p < 0.1 borderline significant. For the multiple comparisons, hypothesis testing was performed using the Bonferroni correction (the p-value divided by

Gender and clinical forms and symptoms at onset and diagnosis

We analyzed 627 WD patients — 337 men and 290 women. At diagnosis, there were 510 (83%) clinically symptomatic patients (278 men and 232 women, p < 0.05) and 104 (16.9%) presymptomatic patients (13 patients were unclassified because of too little clinical data).

At symptom onset, there were 303 (59%) patients with neuropsychiatric and 204 (40%) patients with the hepatic form of the disease. There was a higher (p < 0.01) occurrence of the neuropsychiatric form in men (67%, 189/278 cases) compared to

Discussion

This study, based on data from 627 patients, is the one of the largest studies of gender differences in WD patients. We determined the significant gender differences that occurred in the clinical presentation of WD patients. In our population, we found more WD men than women (53.74% vs. 46.25%; p < 0.05) and neuropsychiatric forms of WD occurred more frequently than hepatic forms (67% vs. 32%). We determined the gender differences in the course of WD were: 1) the neuropsychiatric form of WD was

Conflict of interest

The authors declare not potential conflict of interests relevant to this article.

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