Wilson's disease

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Wilson disease's is a rare autosomal recessive genetic disease characterized by abnormal copper transportation. Its' presentation may be atypical. In the context of pathology, it is typically seen as a liver biopsy.

General

Epidemiology:

  • Rare autosomal recessive - mutation in copper-transporting adenosine triphosphatase (ATPase) gene (ATP7B).[1][2]
    • Heterozygote carrier rate approximately 1/100 persons.[1]
  • Young individuals - usually 12-23 years old.
    • May have late-onset (symptomatic when >40 years old).[3]

Clinical:

  • Kayser-Fleischer rings --> on slit-lamp examination (green eyes).
  • May present to psychiatry or appear to be abusing EtOH.
  • Serum ceruloplasmin - lower than normal; typical value for Wilson's ~ 0.12 g/L.
    • <0.20 g/L is a criteria for Wilson's disease.[4]

Etiology:

  • Excess copper -- due to genetic defect.

Microscopic

Features:

A. Inflamed & relatively unaffected segments  (40X).
B. Bile ductular proliferation with interface hepatitis [inflammation of periportal hepatocytes]  (200X).
C. Enlarged hepatocytes, some with feathery degeneration, others with steatosis. Nuclei show nucleoli (400X).
D. Trichrome shows periportal & sinusoidal fibrosis. No bridging was seen. (100X).
Wilson’s disease, pre-cirrhotic. A. Inflamed & relatively unaffected segments. B. Bile ductular proliferation with interface hepatitis [inflammation of periportal hepatocytes]. C. Enlarged hepatocytes, some with feathery degeneration, others with steatosis. Nuclei show nucleoli. D. Trichrome shows periportal & sinusoidal fibrosis.

Wilson’s disease with cirrhosis Wilson’s disease with cirrhosis Wilson’s disease with cirrhosis Wilson’s disease with cirrhosis Wilson’s disease with cirrhosis
Wilson’s disease with cirrhosis in a 22 year old woman. A. Nodules show steatosis without definite triads. B. Trichrome shows minute fibrous bound nodules in this case. C. Reticulin shows extensive regeneration (2-3 nuclei thick cords with lack of direction) with nodule formation. D. Bridge with extensive proliferated bile ductules and acute and chronic inflammatory cells. E. Ballooning degeneration with Mallory bodies.

Stains

  • Copper staining positive - only 15% of cases.
    • Other stains: rhodinine (red/orange granules = positive), orecin.

Notes:

  • Copper staining is a non-specific finding seen in many liver diseases; it is associated with impaired bile secretion.[5]

Image

Additional testing

Copper quantification:

  • Mass spectrometry.[6]
  • Atomic absorption spectroscopy.
    • >250 microg of copper/g of liver suggest Wilson's disease; below does not exclude it.[7]

Sensitivity:[8]

  • 250 microg of copper/g of liver - 80-86% (value dependent on sampling).
  • 50 microg of copper/g of liver - 97%.

See also

References

  1. 1.0 1.1 http://emedicine.medscape.com/article/183456-overview
  2. Online 'Mendelian Inheritance in Man' (OMIM) 606882
  3. Ferenci, P.; Członkowska, A.; Merle, U.; Ferenc, S.; Gromadzka, G.; Yurdaydin, C.; Vogel, W.; Bruha, R. et al. (Apr 2007). "Late-onset Wilson's disease.". Gastroenterology 132 (4): 1294-8. doi:10.1053/j.gastro.2007.02.057. PMID 17433323.
  4. Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: http://www.clinchem.org/cgi/reprint/54/8/1356.pdf. Accessed on: 28 September 2009.
  5. Miyamura H, Nakanuma Y, Kono N (December 1988). "Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases". Gastroenterol. Jpn. 23 (6): 633–8. PMID 2464523.
  6. Hahn, SH. (May 2014). "Population screening for Wilson's disease.". Ann N Y Acad Sci 1315: 64-9. doi:10.1111/nyas.12423. PMID 24731025.
  7. Ferenci, P.; Steindl-Munda, P.; Vogel, W.; Jessner, W.; Gschwantler, M.; Stauber, R.; Datz, C.; Hackl, F. et al. (Aug 2005). "Diagnostic value of quantitative hepatic copper determination in patients with Wilson's Disease.". Clin Gastroenterol Hepatol 3 (8): 811-8. PMID 16234011.
  8. Liggi, M.; Mais, C.; Demurtas, M.; Sorbello, O.; Demelia, E.; Civolani, A.; Demelia, L. (Dec 2013). "Uneven distribution of hepatic copper concentration and diagnostic value of double-sample biopsy in Wilson's disease.". Scand J Gastroenterol 48 (12): 1452-8. doi:10.3109/00365521.2013.845904. PMID 24164422.

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