Wilson's disease or hepatolenticular degeneration is an autosomal recessivehereditary disease, with an incidence of about 1 in 30,000 in most parts of the world and a male preponderance. Its main feature is accumulation of copper in tissues, which manifests itself with neurological symptoms and liver disease. The estimated heterozygouscarrier rate is about 1 in 9,000, meaning that 1 in 9,000 people are unaffected carriers of this mutation.
Signs and symptoms
Wilson's disease is inherited in an autosomal recessive fashion.
Symptoms usually appear around the ages of 18 to 21 years, but sometimes not until the age of 30, and in rare instances up to age 50. Presentation before 5 years of age is extremely rare, despite the biochemical defect being present at birth.
The age of presentation seems to correlate with the organ system involved. About half (40–50%) of patients first present with hepatic symptoms and half (40–50%) with neurologic symptoms. The average age for hepatic symptoms is 10–14 years, compared with 19–22 years for neurologic symptoms. Patients rarely present after age 40.
A suppressed level of ceruloplasmin is present in over 80% of patients, and this is commonly performed as a screening test in patients with liver problems. A more accurate measurement is the direct testing for copper levels in a 24h specimen of urine, in the blood or in the sample obtained by liver biopsy. The average concentration of hepatic copper may reach 20 times normal levels, whilst plasma ceruloplasmin levels are typically less than 30% of normal.
An eye exam would detect the Kayser-Fleischer ring, although its absence does not rule out Wilson's and it may be missed on cursory examination. This sign is characterised by brown rings around the cornea in the eye that result from copper deposition in Descemet's membrane of the cornea.
The disease is treated with lifelong use of chelating agents such as D-penicillamine or trientine hydrochloride, drugs that help remove copper from tissue. Patients will also need to take vitamin B6 and follow a low-copper diet, which means avoiding mushrooms, nuts, chocolate, dried fruit, liver, and shellfish. Taking extra zinc may be helpful in blocking the intestines' absorption of copper.
Liver transplantation is effective in patients with fulminant Wilson's disease that does not respond to the usual treatment. Because the primary defect resides within the liver, transplantation is curative, but as it is only undertaken in severely ill patients the prognosis is still mediocre.
In Western populations the incidence is around 1 per 30,000, with a carrier rate of 1 in 9,000. The gene frequency is much higher in Hispanics, especially in Central America, and in El Salvador, the indicence is 1 in 186. In Usulután Department, El Salvador it has been reported that 1 in 4 persons carry the disease.
The disease bears the name of the British physician Dr Samuel Alexander Kinnier Wilson (1878-1937), who described the condition in 1912. Dr J.N. Cumings made the link with copper accumulation in 1948. The first effective chelation agent, penicillamine, was discovered in 1956 by Dr John Walshe. The genetic basis was elucidated in the 1980s and 1990s by several research groups.