Difference between revisions of "Wilson's disease"

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#redirect [[Medical_liver_disease#Wilson.27s_disease]]
'''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).<ref name=emedicine183456>[http://emedicine.medscape.com/article/183456-overview http://emedicine.medscape.com/article/183456-overview]</ref><ref name=omim606882>{{OMIM|606882}}</ref>
**Heterozygote carrier rate approximately 1/100 persons.<ref name=emedicine183456/>
*Young individuals - usually 12-23 years old.
**May have late-onset (symptomatic when >40 years old).<ref name=pmid17433323>{{Cite journal  | last1 = Ferenci | first1 = P. | last2 = Członkowska | first2 = A. | last3 = Merle | first3 = U. | last4 = Ferenc | first4 = S. | last5 = Gromadzka | first5 = G. | last6 = Yurdaydin | first6 = C. | last7 = Vogel | first7 = W. | last8 = Bruha | first8 = R. | last9 = Schmidt | first9 = HT. | title = Late-onset Wilson's disease. | journal = Gastroenterology | volume = 132 | issue = 4 | pages = 1294-8 | month = Apr | year = 2007 | doi = 10.1053/j.gastro.2007.02.057 | PMID = 17433323 }}</ref>
 
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.<ref name=pmid18556333>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 http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
 
Etiology:
*Excess copper -- due to genetic defect.
 
==Microscopic==
Features:
*Nothing specific - known as the great mimicker of [[liver pathology]].
*[[Steatosis of the liver|Steatosis]].
*Portal fibrosis.
 
A. [[File:1 Wilson 1 680x512px.tif|Inflamed & relatively unaffected segments  (40X).]]<br>
B. [[File:2 Wilson 1 680x512px.tif|Bile ductular proliferation with interface hepatitis [inflammation of periportal hepatocytes]  (200X).]]<br>
C. [[File:3 Wilson 1 680x512px.tif|Enlarged hepatocytes, some with feathery degeneration, others with steatosis. Nuclei show nucleoli (400X).]]<br>
D. [[File:4 Wilson 1 680x512px.tif|Trichrome shows periportal & sinusoidal fibrosis. No bridging was seen. (100X).]]<br>
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.
 
[[File:4 38555059990939 sl 1.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 2.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 3.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 4.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 5.png|Wilson’s disease with cirrhosis]] <br>
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.<ref name=pmid2464523>{{cite journal |author=Miyamura H, Nakanuma Y, Kono N |title=Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases |journal=Gastroenterol. Jpn. |volume=23 |issue=6 |pages=633–8 |year=1988 |month=December |pmid=2464523 |doi= |url=}}</ref>
 
===Image===
*[http://openi.nlm.nih.gov/legacy/detailedresult.php?img=3375662_yjbm_85_2_249_g03&req=4 Orecin staining in Wilson's diseae (nih.gov)].
 
==Additional testing==
Copper quantification:
*Mass spectrometry.<ref name=pmid24731025>{{Cite journal  | last1 = Hahn | first1 = SH. | title = Population screening for Wilson's disease. | journal = Ann N Y Acad Sci | volume = 1315 | issue =  | pages = 64-9 | month = May | year = 2014 | doi = 10.1111/nyas.12423 | PMID = 24731025 }}</ref>
*Atomic absorption spectroscopy.
**>250 microg of copper/g of liver suggest Wilson's disease; below does not exclude it.<ref name=pmid16234011>{{Cite journal  | last1 = Ferenci | first1 = P. | last2 = Steindl-Munda | first2 = P. | last3 = Vogel | first3 = W. | last4 = Jessner | first4 = W. | last5 = Gschwantler | first5 = M. | last6 = Stauber | first6 = R. | last7 = Datz | first7 = C. | last8 = Hackl | first8 = F. | last9 = Wrba | first9 = F. | title = Diagnostic value of quantitative hepatic copper determination in patients with Wilson's Disease. | journal = Clin Gastroenterol Hepatol | volume = 3 | issue = 8 | pages = 811-8 | month = Aug | year = 2005 | doi =  | PMID = 16234011 }}</ref>
 
[[Sensitivity]]:<ref>{{Cite journal  | last1 = Liggi | first1 = M. | last2 = Mais | first2 = C. | last3 = Demurtas | first3 = M. | last4 = Sorbello | first4 = O. | last5 = Demelia | first5 = E. | last6 = Civolani | first6 = A. | last7 = Demelia | first7 = L. | title = Uneven distribution of hepatic copper concentration and diagnostic value of double-sample biopsy in Wilson's disease. | journal = Scand J Gastroenterol | volume = 48 | issue = 12 | pages = 1452-8 | month = Dec | year = 2013 | doi = 10.3109/00365521.2013.845904 | PMID = 24164422 }}</ref>
*250 microg of copper/g of liver - 80-86% (value dependent on sampling).
*50 microg of copper/g of liver - 97%.
 
==See also==
*[[Medical liver disease]].
 
==References==
{{Reflist|2}}
 
==External links==
*[https://www.lhsc.on.ca/lab/metals/req.htm Trace metals laboratory (lhsc.on.ca)].
 
[[Category:Medical liver disease]]
[[Category:Diagnosis]]

Latest revision as of 19:17, 9 January 2017

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.

External links

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