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

Study Objectives: 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. Methods: 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. Results: 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. Conclusions: Our study indicates that sleep disorders are frequent in patients with WD. Future studies should examine the longitudinal association of WD with sleep disturbances.