Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in ATP7B. R778L is the most common ATP7B mutation in China.
To estimate whether R778L is associated with the onset age of WD and other clinical variables. Genotyping results of ATP7B gene were collected in our 22 patients with WD. We then conducted a systematic review and meta-analysis in databases, using the keywords Wilson disease and R778L mutation.
After the screening, a total of 23 studies were included, including 3007 patients with WD. Patients with R778L mutation presented at an earlier age (standardized mean difference [SMD] = -0.18 [95% confidence interval, -0.28 to 0.08], P = 0.0004) and had lower ceruloplasmin concentration (SMD = -0.21 [95% confidence interval, -0.40 to -0.02], P = 0.03) than the patients without the R778L mutation. However, sex (odds ratio [OR] = 1.07 [95% confidence interval, 0.89 to 1.29], P = 0.32) and first presentation were not associated with R778L mutation in WD (hepatic: OR = 1.37 [95% confidence interval, 0.87 to 2.16, P = 0.17; neurological: OR = 0.79 [95% confidence interval, 0.48 to 1.30, P = 0.35; mix: OR = 1.04 [95% confidence interval, 0.42 to 2.53, P = 0.87; asymptomatic/others: OR = 1.98 [95% confidence interval, 0.49 to 7.96, P = 0.34).
Our results indicated that the R778L mutation is associated with an earlier presentation and lower ceruloplasmin concentration in China.

A Systematic Review and Meta-Analysis of the R778L Mutation in ATP7B With Wilson Disease in China.

Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism resulting in pathologic accumulation of copper in many organs and tissues. Sleep disorders are highly prevalent in patients with WD. However, both prevalence rates and severity of different sleep disorders in patients with WD vary widely. The aims of the current study were to systematically review and perform a meta-analysis of the association between WD and prevalent sleep disorders, including insomnia, rapid eye movement (REM) sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), sleep-disordered breathing (SDB), restless legs syndrome (RLS), periodic limb movement in sleep (PLM), cataplexy-like episodes (CLEs) and sleep paralysis, and objective sleep characteristics.
We performed a systematic search of PubMed, EMBase, the Cochrane Library, PsycINFO and ISI Web of Science for case-control studies. A total of 7 studies with 501 participants were included.
We found that 54.1% of patients with WD experience sleep disorders and up to 7.65-fold higher odds compared to control patients. Specifically, patients with WD had higher rates of RBD, insomnia, and EDS based on self-reported questionnaires. No differences were observed in terms of RLS, PLM, or SDB between patients with WD and control patients. Furthermore, objective sleep disruptions based on polysomnographic studies included prolonged sleep onset latency and REM sleep onset latency, reduced total sleep time and sleep efficiency, higher percentage of stage N1 sleep and lower percentage of stage N2 sleep were observed in patients with WD.
Our study indicates that sleep disorders are frequent in patients with WD. Future studies should examine the longitudinal association of WD with sleep disturbances.

Sleep disorders in Wilson disease: a systematic review and meta-analysis.

Growing evidences have implied that patients with primary breast cancer (BC) were at increased risks of developing diabetes mellitus (DM). However, as a major adjuvant treatment, the influence of hormone therapy (HT) on secondary DM in primary BC remains controversial; we conducted a meta-analysis of existing studies to evaluate the association of hormone therapy and secondary DM.
We searched online databases (PubMed, EMBASE, the Cochrane library, Scopus, and Google Scholar) for studies exploring the influence of hormone therapy on secondary DM in BC. The summarized effect sizes (ES) and 95% confidence interval (95% CI) are calculated by STATA software utilizing fixed-effect or random-effect models, depending on the heterogeneity of the eligible studies.
Ultimately, 7 retrospective publications including a total of 44,524 primary BC patients are eligible in present meta-analysis. HT use significantly increased the risk of developing DM in primary BC patients, whenever compared with NON-HT BC patients (pooled adjusted HR 1.30, 95% CI: 1.19-1.43) or NORMAL participants (HR 1.19, 95% CI: 1.14-1.25). As to specific HT medications, our sub-analysis demonstrates the risk for DM in tamoxifen (TAM) users elevates by 30% than NON-TAM use BC patients (pooled HR 1.30, 95% CI: 1.20-1.40) and by 18% than NORMAL participants (pooled HR 1.18, 95% CI: 1.12-1.24). However, for aromatase inhibitors (AIs) users, the risks for DM do not elevate significantly. Funnel plots and Egger's tests are used to evaluate publication bias and no apparent bias is detected in all analysis.
The present study is the first meta-analysis which thoroughly reveals that adjuvant HT is a risk factor of secondary DM in primary female BC patients. As to specific HT medications, TAM use significantly enhances the incidence of secondary DM, while AIs use does not influence the DM incidence significantly. Our results can help clinicians to tailor more appropriate strategies for the therapy and follow-up of primary BC patients.

Papers