Wilson disease, also known as hepatolenticular degeneration, is a rare autosomal recessive disorder of copper metabolism affecting multiple systems.
Wilson disease is commonly found in Japan. It affects 1 in 30,000-40,000 individuals 12. 1 in 90 individuals are a heterozygous carrier 18.
Clinical presentation is non-specific and varied, typically manifesting by early adulthood 5,11,13,15:
- weakening of hands and dysarthria are often the earliest symptoms 5
- pseudoparkinsonian and cerebellar symptoms
- psychiatric symptoms
- liver disease (tends to be seen in early-onset presentations)
Asymptomatic Kayser-Fleischer rings are usually seen in the cornea and are a characteristic feature 11.
It is a disorder that results from abnormal ceruloplasmin metabolism, as a result of a variety of mutations in the ATP7B gene. Total body copper is elevated that has toxic effects on hepatocytes with copper deposition and resulting damage to a variety of organs, e.g. liver and brain.
Three pathways affected mostly:
- dentatorubrothalamic tract
- pontocerebellar tract
- corticospinal tract
- serum ceruloplasmin: reduced 13,14
- serum copper: reduced 14
- free serum copper: increased 14
- urinary copper: increased 14
Please see individual articles:
- Wilson disease: hepatobiliary manifestations
- Wilson disease: CNS manifestations
- Wilson disease: musculoskeletal manifestations
Treatment and prognosis
Treatment options include chelation therapy which includes zinc, trientine, and penicillamine 7,18.
History and etymology
It was initially described by Samuel Alexander Kinnier Wilson, an American neurologist, in 1912 as "progressive lenticular degeneration" 10. Interestingly, Kayser-Fleischer rings were initially described a decade earlier by German physicians Bernhard Kayser and Bruno Fleischer in 1902 and 1903 respectively 16,17.
- 1. Boon NA, Colledge NR, Davidson SS et-al. Davidson's principles & practice of medicine. Churchill Livingstone. (2006) ISBN:0443100578. Read it at Google Books - Find it at Amazon
- 2. Aisen AM, Martel W, Gabrielsen TO et-al. Wilson disease of the brain: MR imaging. Radiology. 1985;157 (1): 137-41. Radiology (abstract) - Pubmed citation
- 3. Kim TJ, Kim IO, Kim WS et-al. MR imaging of the brain in Wilson disease of childhood: findings before and after treatment with clinical correlation. AJNR Am J Neuroradiol. 27 (6): 1373-8. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 4. Kvícala V, Vymazal J, Nevsimalová S. Computed tomography of Wilson disease. AJNR Am J Neuroradiol. 4 (3): 429-30. AJNR Am J Neuroradiol (abstract) - Pubmed citation
- 5. King AD, Walshe JM, Kendall BE et-al. Cranial MR imaging in Wilson's disease. AJR Am J Roentgenol. 1996;167 (6): 1579-84. AJR Am J Roentgenol (abstract) - Pubmed citation
- 6. Tani I, Kurihara Y, Kawaguchi A et-al. MR imaging of diffuse liver disease. AJR Am J Roentgenol. 2000;174 (4): 965-71. AJR Am J Roentgenol (full text) - Pubmed citation
- 7. Walshe JM, Yealland M. Chelation treatment of neurological Wilson's disease. Q. J. Med. 1993;86 (3): 197-204. Q. J. Med. (abstract) - Pubmed citation
- 8. De maria M, De simone G, Laconi A et-al. Gold storage in the liver: appearance on CT scans. Radiology. 1986;159 (2): 355-6. Radiology (abstract) - Pubmed citation
- 9. Runge VM, Clanton JA, Smith FW et-al. Nuclear magnetic resonance of iron and copper disease states. AJR Am J Roentgenol. 1983;141 (5): 943-8. AJR Am J Roentgenol (abstract) - Pubmed citation
- 10. Wilson SAK. Progressive lenticular degenerations: A familial nervous disease associated with cirrhosis of the liver. (1912) Brain. 34 (4): 295. doi:10.1093/brain/34.4.295
- 11. Hegde AN, Mohan S, Lath N et-al. Differential diagnosis for bilateral abnormalities of the basal ganglia and thalamus. Radiographics. 31 (1): 5-30. doi:10.1148/rg.311105041 - Pubmed citation
- 12. Patil M, Sheth KA, Krishnamurthy AC et-al. A review and current perspective on Wilson disease. J Clin Exp Hepatol. 2013;3 (4): 321-36. doi:10.1016/j.jceh.2013.06.002 - Free text at pubmed - Pubmed citation
- 13. Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47 (6): 2089-111. doi:10.1002/hep.22261 - Pubmed citation
- 14. Kumar N, Butz JA, Burritt MF. Clinical significance of the laboratory determination of low serum copper in adults. Clin. Chem. Lab. Med. 2007;45 (10): 1402-10. doi:10.1515/CCLM.2007.292 - Pubmed citation
- 15. Lorincz MT. Neurologic Wilson's disease. (2010) Annals of the New York Academy of Sciences. 1184: 173-87. doi:10.1111/j.1749-6632.2009.05109.x - Pubmed
- 16. Kayser B. Über einen Fall von angeborener grünlicher Verfärbung des Cornea. (1902) Klin Monatsbl Augenheilk. 40 (2): 22–25.
- 17. Fleischer B. Zwei weitere Fälle von grünlicher Verfärbung der Kornea.(1903) Klin Monatsbl Augenheilk. 41(1):489–491.
- 18. Wolfgang F. Dahnert. Radiology Review Manual. (2020) ISBN: 9781496360694
- 19. Guindi M, Guindi. Wilson Disease. (2019) Seminars in diagnostic pathology. doi:10.1053/j.semdp.2019.07.008 - Pubmed