Wilson disease

Abstract

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. Since daily copper intake exceeds the body's requirements, effective means of excreting excess copper are essential. These are accomplished by ATP7B, a new member of the cation-transporting p-type ATPase family, which is mainly expressed in the liver and mediates both copper secretion into plasma (coupled with ceruloplasmin synthesis) and its excretion into bile. Thus far, more than 200 mutations of the WD gene have been detected, causing impairment of ATP7B function and, ultimately, copper accumulation. Excess copper, however, induces free-radical reactions and lipid peroxidation. Resultant liver damage leads to steatosis, inflammation, cirrhosis, and, occasionally, fulminant liver failure. The diagnosis of WD is commonly made on the basis of typical clinical and laboratory findings, including low serum ceruloplasmin, increased urinary copper excretion, and increased hepatic copper content. Since liver morphology is non-specific, and copper histochemistry may lead to both false-negative and false-positive results, the pathologist usually only suspects the disease or assists in its confirmation. Although the value of molecular genetic testing is limited due to the high number of possible gene mutations, polymerase chain reaction may be useful for the evaluation of family members of homozygous index patients.

Increased copper levels in in vitro and in vivo models of Niemann-Pick C disease

“…An increase in copper, iron or zinc levels has been described as a risk factor for oxidative stress damage in neurodegenerative pathologies such as amiotrophic lateral sclerosis, Alzheimer's Disease and Parkinson's Disease (Barnham and Bush 2008). Furthermore, mutations in copperbinding proteins have been linked to those devastating disorders (Gaggelli et al 2006) as well as Wilson disease and Menkes disease (Kaler 1994;Langner and Denk 2004). Therefore, appropriate levels of copper are essential to avoid cellular damage by oxidative stress due to the rapid oxidation of copper, which causes damage to the biomolecules listed above and generates ROS, leading to cell death (Linder 1991).…”

Hepatic copper-transporting ATPase ATP7B: function and inactivation at the molecular and cellular level

“…Disruption of ATP7B function has dramatic consequences for liver function and overall copper metabolism. In patients with Wilson disease (WD) both copper delivery to the secretory pathway and biliary excretion are disrupted due to mutations in ATP7B [18]. As a result, copper accumulates in the liver and other tissues, which lead to a spectrum of liver pathologies, neurological abnormalities, and, if left untreated, death.…”

Febrile Syndrome as a First Clinical Manifestation of Wilson Disease

“…Although in patients with the classical manifestations described by Kinnear Wilson in 1912 characterized by Kayser-Fleischer rings, neurological and hepatic symptoms the diagnosis seems to be easy [1,4], it is a challenge in those patients with atypical manifestations [5,6], such as our patient. The clinical manifestations are varied so the diagnostic is often difficult and delayed.…”