Neurological Wilson’s Disease Signs—Hepatic Encephalopathy or Copper Toxicosis?

Abstract

Wilson’s disease (WD) is a rare autosomal recessive (AR) disorder resulting from mutations in the ATP7B gene, which is responsible for the encryption of transmembrane copper transporting ATPase. The symptomatic presentation of the disease is estimated to be about 1 in 30,000. The impairment of ATP7B function results in a copper overload in hepatocytes, which further leads to liver pathology. This copper overload also occurs in other organs, most particularly in the brain. This could then cause the occurrence of neurological and psychiatric disorders. Symptoms differ substantially and most often occur between the ages of 5 and 35 years. Early symptoms are commonly hepatic, neurological, or psychiatric. While disease presentation is most often asymptomatic, it could also range as far as to include fulminant hepatic failure, ataxia, and cognitive disorders. Various treatments are available for Wilson’s disease, including chelation therapy and zinc salts, which can reverse copper overload through different mechanisms. In select cases, liver transplantation is recommended. New medications, such as tetrathiomolybdate salts, are currently being investigated in clinical trials. With prompt diagnosis and treatment, prognosis is favorable; however, diagnosing patients before the onset of severe symptoms is a significant concern. Early screening for WD could help in diagnosing patients earlier and improving treatment outcomes.

Comprehensive analysis of Cuproplasia and immune microenvironment in lung adenocarcinoma

“…Clinical evidence further underscores the importance of copper in cancer development. Specifically, abnormal copper accumulation in Wilson disease patients fosters malignant transformation of liver cells ( Jopowicz and Tarnacka, 2023 ). Moreover, the Mitogen-activated protein kinases (MAPK) signaling pathways, which are intimately involved in the development of various cancers ( Turski et al, 2012 ), are influenced by copper levels.…”

Health-Related Quality of Life in Patients Living with Wilson Disease in Spain: A Cross-Sectional Observational Study

“…Liver involvement is the norm among children and can vary from asymptomatic, presenting only biochemical abnormalities, to acute hepatitis or liver failure, chronic hepatitis, or clinical decompensation of cirrhosis [5,6]. Neurological and psychiatric symptoms are more frequent in young adults aged 20-30 years [9], affecting approximately 20-65% of patients with WD [10]. The most frequent neurological symptoms are tremor, dystonia, Parkinsonism, dysarthria, dysphagia, drooling, and epilepsy [11].…”

“…The most frequent neurological symptoms are tremor, dystonia, Parkinsonism, dysarthria, dysphagia, drooling, and epilepsy [11]. Psychiatric symptoms can arise before, concurrent with, or after WD diagnosis and treatment [12], and may include personality changes, mood (mania, depression, anxiety) and sleep disturbances, cognitive deficits, and psychosis [9,11]. It is estimated that up to 70% of patients with WD may present with psychiatric involvement at some time [13].…”