Wilson’s disease: a rare disorder with complex liver and neurological impacts

Wilson’s disease (WD), an inherited disorder characterized by abnormal copper metabolism, manifests through diverse hepatic, neurological, and psychiatric symptoms. Identified first in 1912 as “progressive lenticular degeneration,” this autosomal recessive condition results from ATP7B gene mutations, leading to copper accumulation primarily in the liver and brain. Prevalence estimates vary, with current figures suggesting about 1 in 30,000 to 1 in 50,000 globally, though genetic data imply higher subclinical rates.

Hepatic symptoms often surface in childhood, ranging from asymptomatic liver test abnormalities to acute liver failure (ALF), a critical condition representing up to 5% of global ALF cases. Neurological signs, such as dysarthria, tremor, and dystonia, can appear later, affecting nearly 40–60% of patients and mimicking other movement disorders. Psychiatric manifestations contribute to WD’s reputation as a “great masquerader,” presenting with depression, cognitive decline, or psychosis.

Diagnosis leverages clinical assessment, serologic testing, liver biopsy, and genetic screening. The Leipzig scoring system aids in confirming WD, combining findings like low ceruloplasmin, Kayser-Fleischer rings, and urinary copper levels. Treatment includes lifelong copper-chelating agents such as D-penicillamine and trientine, or zinc to prevent copper absorption. In advanced hepatic cases, liver transplantation may be lifesaving, with promising outcomes and potential neurological improvements reported.

Emerging therapies, including gene therapy targeting ATP7B functionality, are under investigation, hinting at future advancements. Early diagnosis and adherence to treatment are critical to preventing irreversible damage and achieving outcomes comparable to those of the general population.