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 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, liver disease, neurologic conditions, or psychiatric disorders.

Investigate all patients with liver function tests, slit lamp exam for Kayser-Fleischer rings, serum ceruloplasmin, and 24-hour urinary copper measurement. Further investigations (e.g., genetic testing for ATP7B mutations, liver biopsy) may be indicated. No test is capable of diagnosing Wilson disease in isolation. The Leipzig score compiles clinical features and investigation results; a score ≥4 is diagnostic.

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. Patients with acute hepatic failure should be urgently assessed for liver transplant.

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 ​ Wilson disease can present as liver disease, a progressive neurologic disorder, a psychiatric illness, or a combination of all of these.[5]Schilsky ML, Roberts EA, Bronstein JM, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: executive summary of the 2022 practice guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2023 Apr 1;77(4):1428-55. https://journals.lww.com/hep/fulltext/2023/04000/a_multidisciplinary_approach_to_the_diagnosis_and.32.aspx http://www.ncbi.nlm.nih.gov/pubmed/36152019?tool=bestpractice.com ​​