Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease. It is treated with medication that reduces copper absorption or removes the excess copper from the body, but occasionally a liver transplant is required. Patients with liver problems tend to come to medical attention earlier, generally as children or teenagers, than those with neurological and psychiatric symptoms, who tend to be in their twenties or older. Some are identified only because relatives have been diagnosed with Wilson's disease; many of these patients, when tested, turn out to have been experiencing symptoms of the condition but haven't received a diagnosis.
Liver disease may present as tiredness, increased bleeding tendency or confusion (due to hepatic encephalopathy) and portal hypertension. The latter, a condition in which the pressure on the portal vein is markedly increased, leads to esophageal varices (blood vessels in the esophagus) that may bleed in a life-threatening fashion, splenomegaly (enlargement of the spleen) and ascites (accumulation of fluid in the abdominal cavity). On examination, signs of chronic liver disease such as spider naevi (small distended blood vessels, usually on the chest) may be observed. Chronic active hepatitis has caused cirrhosis of the liver in most patients by the time they develop symptoms. While most people with cirrhosis have an increased risk of hepatocellular carcinoma (liver cancer), this risk is relatively very low in Wilson's disease. If there are neurological symptoms, magnetic resonance imaging (MRI) of the brain is usually performed; this shows hyperintensities in the part of the brain called the basal ganglia in the T2 setting. MRI may also demonstrate the characteristic "face of the giant panda" pattern.
There is no totally reliable test for Wilson's disease, but levels of ceruloplasmin and copper in the blood, as well of the amount of copper excreted in urine during a 24 hour period, are together used to form an impression of the amount of copper in the body. The gold standard or most ideal test is a liver biopsy.
A normal variation in the ''PRNP'' gene can modify the course of the disease by delaying the age of onset and affecting the type of symptoms that develop. This gene produces prion protein, which is active in the brain and other tissues and also appears to be involved in transporting copper. A role for the ''ApoE'' gene was initially suspected but could not be confirmed.
Wilson's Disease Treatment
Various treatments are available for Wilson's disease. Some increase the removal of copper from the body, while others prevent the absorption of copper from the diet. In general, a diet low in copper-containing foods (mushrooms, nuts, chocolate, dried fruit, liver, and shellfish) is recommended.. These drugs binds copper (chelation) and leads to excretion of copper in the urine. Hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. The reason penicillamine is used less, is because about 20% of patients experience a side effect or complication of penicillamine treatment, such as drug-induced lupus (causing joint pains and a skin rash) or myasthenia (a nerve condition leading to muscle weakness). In those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. While this phenomenon is also observed in other treatments for Wilson's, it is usually an indication for discontinuing penicillamine or not starting it in the first place.
People who are asymptomatic (for instance those diagnosed through family screening or only as a result of abnormal test results) are generally treated, as the copper accumulation may cause long-term damage in the future. It is unclear whether these people are best treated with penicillamine or zinc acetate. where it generally only affects the liver. It is due to mutations in the ''COMMD1'' (or ''MURR1'') gene. In patients with non-Wilsonian copper accumulation states (such as Indian childhood cirrhosis), no ''COMMD1'' mutations could be detected to explain their genetic origin.
Wilson's Disease History
The disease bears the name of the British physician Dr Samuel Alexander Kinnier Wilson (1878-1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912. Wilson's work had been predated by, and drew on, reports from the German neurologist Dr Carl Westphal (in 1883), who termed it "pseudosclerosis", by the British neurologist Dr William Gowers (in 1888), and by Dr Adolph Strümpell (in 1898), who noted hepatic cirrhosis. Prof John N. Cumings made the link with copper accumulation in both the liver and the brain in 1948. The occurrence of hemolysis was noted in 1967.
Cumings, and simultaneously the New Zealand neurologist Dr Derek Denny-Brown, working in the USA, first reported effective treatment with metal chelator British anti-Lewisite in 1951. This treatment had to be injected but was one of the first therapies available in the field of neurology, a field that classically was able to observe and diagnose but had few treatments available. The first effective oral chelation agent, penicillamine, was discovered in 1956 by the British neurologist Dr John Walshe. In 1982, Walshe also introduced trientine, and was the first to develop tetrathiomolybdate for clinical use. Zinc acetate therapy initially made its appearance in the Netherlands, where physicians Schouwink and Hoogenraad used it in 1961 and in the 1970s, respectively, but it was further developed later by Brewer and colleagues at the University of Michigan.
The genetic basis of Wilson's disease and linkage to ATP7B mutations was elucidated in the 1980s and 1990s by several research groups.
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