Wilson's Disease Coexisting with Narcolepsy Type 1: Evidence for a Multifactorial Cause of Excessive Daytime...

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism that frequently involves the central nervous system and may be associated with secondary sleep disturbances. Excessive daytime sleepiness (EDS) in WD is typically attributed to metabolic or structural brain injury rather than primary sleep-wake dysregulation. Narcolepsy type 1 (NT1), caused by autoimmune loss of hypothalamic hypocretin neurons, is a distinct primary sleep disorder. The coexistence of WD and NT1 has not previously been reported.

We describe a 23-year-old woman with a 15-year history of WD who developed long-standing EDS accompanied by emotionally triggered cataplexy, sleep paralysis, and hypnagogic hallucinations. Genetic analysis identified pathogenic ATP7B variants (p.R778L and p.R919G). Brain MRI revealed symmetric signal abnormalities involving the basal ganglia, midbrain nuclei, cerebellar dentate nuclei, and hypothalamus, suggesting chronic neurotoxicity. Comprehensive sleep evaluation supported a diagnosis clinically consistent with NT1, further corroborated by HLA-DQB1*06:02 positivity. Importantly, hepatic encephalopathy and other secondary causes of hypersomnolence were excluded.

This case suggests the possibility that NT1 can coexist with WD as an independent primary sleep disorder rather than a secondary manifestation of metabolic or structural brain disease. The findings support a multifactorial neurobiological mechanism in which copper-related neurotoxicity and genetic susceptibility converge on hypothalamic injury. Clinicians should maintain a high index of suspicion for primary sleep-wake disorders when patients with WD present with cataplexy or other REM-related symptoms, as accurate differentiation has important implications for diagnosis, management, and prognosis. Infographic available for this article. INFOGRAPHIC.