The Role of Zinc in the Treatment of Wilson’s Disease

Abstract

Wilson’s disease (WD) is a hereditary disorder of copper metabolism, producing abnormally high levels of non-ceruloplasmin-bound copper, the determinant of the pathogenic process causing brain and hepatic damage and dysfunction. Although the disease is invariably fatal without medication, it is treatable and many of its adverse effects are reversible. Diagnosis is difficult due to the large range and severity of symptoms. A high index of suspicion is required as patients may have only a few of the many possible biomarkers. The genetic prevalence of ATP7B variants indicates higher rates in the population than are currently diagnosed. Treatments have evolved from chelators that reduce stored copper to zinc, which reduces the toxic levels of circulating non-ceruloplasmin-bound copper. Zinc induces intestinal metallothionein, which blocks copper absorption and increases excretion in the stools, resulting in an improvement in symptoms. Two meta-analyses and several large retrospective studies indicate that zinc is equally effective as chelators for the treatment of WD, with the advantages of a very low level of toxicity and only the minor side effect of gastric disturbance. Zinc is recommended as a first-line treatment for neurological presentations and is gaining acceptance for hepatic presentations. It is universally recommended for lifelong maintenance therapy and for presymptomatic WD.

Copper-binding proteins genes set predicting the overall survival and immune infiltration in hepatocellular carcinoma by bioinformatic analysis

“…However, the disruption of Cu homeostasis could also lead to the accumulation of reactive oxygen species and proteasome inhibition, causing cellular toxicity [ 39 ]. Abnormal accumulation of Cu was previously reported to be associated with the development of several disease, such as wilson's disease and neuroinflammation [ 40 , 41 ]. Recently, increasing number of studies have revealed that Cu metabolic reprogramming and Cu-dependent cellular process are crucial for cancer development, and it is important to uncover the underlying regulatory mechanisms of Cu in cancer development.…”

Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders

“…Recent genetic diagnosis techniques and their easy accessibility raise the possibility of detecting some metabolic diseases involving Wilson’s disease (WD)[ 13 ], glycogen storage disease (GSD)[ 14 ] and α1-antitrypsin deficiency[ 15 ]. The incidence of WD is usually quoted as 1:30000, but recent genetic studies have shown a higher prevalence ranging from 1:2400 to 1:6500[ 16 ]. CLD affects approximately 1/2500 infants, and biliary atresia accounts for 1/3[ 17 ]; genetic or metabolic factors account for approximately one-third of cholestasis cases causing subsequent liver dysfunction, including citrin deficiency (CD)[ 18 ], progressive familial intrahepatic cholestasis (PFIC)[ 19 ] and Alagille syndrome (AGS)[ 20 ].…”

Wilson’s disease - a current approach to diagnostics and treatment. A literature review

“…[3,11] Sole cynku zmniejszają wchłanianie miedzi przez układ pokarmowy oraz zwiększają jej wydalanie z kałem. [13,14] Stosowane są zarówno w początkowym okresie leczenia, jak i przewlekle w podtrzymywaniu prawidłowego stężenia miedzi w ustroju. [12] Głównym działaniem niepożądanym terapii solami cynku jest dyspepsja.…”