Wilson disease

Wilson disease is an autosomal-recessive disease of copper accumulation and toxicity caused by a defect in an enzyme involved in the excretion of excess copper.

Estimated prevalence is 1 in 30,000 to 1 in 50,000, with no sex or ethnic predominance.

Wilson disease is a systemic disease that can often mimic other conditions, commonly leading to delayed diagnosis or misdiagnosis. It should be considered in patients with abnormal liver enzymes, cirrhosis, neurologic conditions, or psychiatric disorders.

Screening and diagnostic tests: 24-hour urine copper measurement, ophthalmologic slit-lamp examination for Kayser-Fleischer (KF) rings, blood ceruloplasmin levels, serum copper, and liver biopsy with measurement of quantitative copper. If available, genetic testing for ATP7B can be done.

Treatment regimens vary depending on the clinical presentation and treatment phase (initial or maintenance). Pharmacologic therapy includes the oral chelators penicillamine (as the D-isomer) and trientine, which increase urinary copper excretion, and zinc salts, which decrease alimentary copper absorption. In certain severe hepatic cases, liver transplantation can be curative.

Wilson disease is an autosomal-recessive disease of copper overload caused by mutations in the ATP7B gene. ATP7B encodes a metal P-type ATPase that facilitates transmembrane transport of copper within hepatocytes.[1]Bull PC, Thomas GR, Rommens JM, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993 Dec;5(4):327-37. http://www.ncbi.nlm.nih.gov/pubmed/8298639?tool=bestpractice.com [2]Tanzi RE, Petrukhin K, Chernov I, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. 1993 Dec;5(4):344-50. http://www.ncbi.nlm.nih.gov/pubmed/8298641?tool=bestpractice.com [3]Shah AB, Chernov I, Zhang HT, et al. Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses. Am J Hum Genet. 1997 Aug;61(2):317-28. https://www.cell.com/ajhg/pdf/S0002-9297(07)64057-9.pdf http://www.ncbi.nlm.nih.gov/pubmed/9311736?tool=bestpractice.com Lack of the protein leads to decreased copper excretion from the liver and copper overload in hepatocytes. When hepatic storage capacity is exceeded, copper is released into the circulation and deposited in other organs.[4]Członkowska A, Litwin T, Dusek P, et al. Wilson disease. Nat Rev Dis Primers. 2018 Sep 6;4(1):21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416051 http://www.ncbi.nlm.nih.gov/pubmed/30190489?tool=bestpractice.com