An autosomal recessive disease of copper metabolism. The abnormal gene has been localized to chromosome 13 and is linked to enzyme esterase -D. The overall disease incidence is 1:200000. In this condition the copper excretion in the bile is reduced resulting in accumulation of copper in the liver, resulting in oxidant injury to liver cell mitochondria. The clinical evidence of liver injury is usually detected after 5 years. Deposition of copper in the extrapyramidal system of the brain can result in subtle neurological symptoms in children and frank abnormalities in adults. Clinical presentation varies from asymptomatic copper accumulation (stage-1), enlargement of liver and spleen, abnormal liver enzymes, acute liver failure or liver cirrhosis with protal hypertension (stage-2), asymptomatic copper in central nervous system(stage-3) and frank neurological symptoms (stage-4).
Typically Ceruloplasmin is low(<20mg/d1), serum copper is low(<80mg/L) an 24 hour urine copper is high (>100mg/24 hours). False positive reports are common. The copper content of liver is the most reliable test. In wilson's disease the copper content is >250 mic.g/Gm of tissue. Another test that adds to value is to estimate the radioactive copper incorporation in ceruloplasmin, which decreased in Wilson's. In clinical terms the brown rings detected at the junction of the cornea and the iris in the superior aspect of the eye (KF rings) may be difficult to detect among Indians without a slit lamp exam. However these do not appear until mid adolescence and are not unique to Wilson's. Any adolescent with normal alkaline phosphatase and raised enzymes and bilurubin as well as those with acute liver failure with intravascular hemolysis should be strongly suspected of Wilson's disease.
Medical therapy is first line in treatment. Penicillamine-D and trientine dihydrochloride, zinc or tetrathiomolybdate are chelating agents used with success. Oral Zinc has also been proven to have a useful role. It is best to avoid foods rich in copper such as seafood, chocolates or nuts. Indications for liver transplant include- failure to improve either liver or neurological function, acute liver failure or cirrhosis with decompensation of function. Raising enzymes, bilurubin and prothrombin time are poor prognostic signs. Jaundice and ascites also correlated with poor prognosis. Results of liver transplantation is impressive. Complete neurological recovery can be anticipated few months after liver transplant. Early detection and treatment of homozygotes can prevent subsequent need for liver transplant.