Wilson's disease: does a neuropsychiatric phenotype without liver involvement truly exist?

INTRODUCTION: Wilson’s disease (WD) is an inherited disorder of copper metabolism resulting in pathological copper accumulation in multiple organs, predominantly the liver, kidneys, and brain, with subsequent organ damage due to copper toxicity. Although the underlying metabolic defect originates in impaired hepatic copper transport with early hepatocellular injury, the currently accepted clinical phenotypic classification of WD distinguishes two major forms based on presenting symptoms: (1) hepatic and (2) neuropsychiatric, including cases without clinically overt liver disease. The aim of this study was to demonstrate, in an autopsy series of WD patients, that liver pathology is invariably present regardless of clinical phenotype. PATIENTS AND METHODS: We analyzed 21 deceased WD patients hospitalized in our department between 1965 and 2025 who underwent complete autopsy examinations. RESULTS: Twenty-one detailed autopsies were available, including 17 patients with a neurologic phenotype and 4 with a hepatic phenotype. Liver cirrhosis was confirmed in all cases (21/21), despite the absence of clinical signs of cirrhosis during life in 3 patients. CONCLUSIONS: In Wilson’s disease, liver pathology is consistently present irrespective of phenotypic presentation. These findings confirm that WD is fundamentally a primary liver disease.