Wilson Disease

 Inability to excrete copper in bile leads to its accumulation in liver and other tissues






Clinical Issues




• Variable presentation
image Acute liver failure, chronic liver disease with fibrosis/cirrhosis, neurologic/neuropsychiatric signs ± Kayser-Fleischer rings

image Copper chelators and zinc are mainstay of medical therapy

– Without treatment, progresses to cirrhosis and death

image Increased serum free copper and urinary copper are characteristic

image Increased hepatic copper concentration is most reliable test and is diagnostic in most cases

• Laboratory tests
image Low serum ceruloplasmin level is characteristic but is neither sensitive nor specific

image Increased serum free copper and urinary copper

image Increased hepatic copper concentration is most reliable test


Microscopic




• Early disease is characterized by steatosis, variably present Mallory hyaline, and glycogenated nuclei
• Intermediate stage is characterized by chronic hepatitis with fibrosis or cirrhosis

• Histologic features on routine staining are very nonspecific, so diagnosis easily missed

• Rhodanine or rubeanic acid stains for copper and orcein or aldehyde fuchsin stains for copper-associated protein may be helpful

image Staining may be very variable within liver; thus negative stain does not exclude disease

image
Kayser-Fleischer Ring
Clinical photograph of Kayser-Fleischer ring shows brown deposits of copper at the periphery of the iris image. (Courtesy S. Uwaydat, MD.) Almost half of patients with Wilson disease lack this finding, however.


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Rhodanine Stain
Red-brown granular staining is seen within hepatocytes on rhodanine stain, characteristic of Wilson disease. However, staining may be focal within the liver, and thus a negative stain does not exclude disease.

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Features of Steatohepatitis
Liver biopsies in Wilson disease frequently show features of steatohepatitis, with steatosis and glycogenated nuclei image .

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Inflammation
Many biopsies from Wilson disease patients show only nonspecific portal-based chronic inflammation, as seen here. Note the rare, large glycogenated nuclei image .


TERMINOLOGY


Synonyms




• Hepatolenticular degeneration


Definitions




• Inherited autosomal recessive inherited mutation of copper transport protein


ETIOLOGY/PATHOGENESIS


Genetic Defect




• Mutations of ATP7B gene, which codes for copper-dependent P-type ATPase, copper transport protein found on Golgi apparatus and on canalicular membrane
image Inability to excrete copper in bile leads to its accumulation in liver and various tissues

image Inability to transport copper into Golgi apparatus makes it unavailable for synthesis of ceruloplasmin, leading to release of apoceruloplasmin into serum and its rapid degradation

– Ceruloplasmin functions as plasma ferroxidase, oxidizing ferrous iron for subsequent transfer to plasma apotransferrin, making it available for hemoglobin biosynthesis

Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Wilson Disease
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