GASTROENTEROLOGY ARTICLE OF THE WEEK

February 26, 2004 

Gitlin JD.  Wilson Disease. Gastroenterology 2003;125:1868-1877 

1.  Clinical presentation of Wilson Disease (WD)

            a.  rarely presents before age 3

            b.  liver disease is the most common initial presenting feature, usually between

age 10-13

            c.  neurologic disease tends to present between around age 20

            d.  30% will present with chronic active hepatitis and no overt evidence of copper

overload

            e.  the presence of Kayser-Fleisher ring establishes the diagnosis of WD

            f.  a normal hepatic tissue copper level excludes WD 

2.  Copper metabolism

            a.  Absorbed by the ileum and proximal colon

            b.  stored in the liver

            c.  biliary excretion is the only physiological route for copper elimination

            d.  ceruloplasmin binds over 95% of the plasma copper

            e.  renal filtration plays an important role in copper metabolism under physiologic

conditions

            f.  copper has an enterohepatic circulation after it is excreted in bile 

True or False 

3.  Congenital absence of ceruloplasmin causes fulminant WD 

4.  Inheritance of WD is autosomal recessive, affected gene is located on chromosome 13 

5.  Kayser-Fleischer rings are present in most symptomatic patients and in almost all patients with fulminant live disease, but may be absent in those with chronic active hepatitis alone 

6.  Patient with congenital absence of ceruloplasmin will have normal copper metabolism associated with iron overload. 

7.  A low serum ceruloplasmin could be an indicator of copper deficiency 

8.  A low serum ceruloplasmin in a newborn is diagnostic for WD 

9.  About 10% of heterozygotes will have decreased ceruloplasmin levels and a small increase in hepatic copper content.  

10.  Liver transplantation cures WD 

11.  Hepatocellular carcinoma is rare in patients with WD-related cirrhosis 

12.  A defect in ATP7b, a copper-transporting P-type ATPase decreases the amount of copper that can be incorporated into ceruloplasmin leading to a low serum level of ceruloplasmin, accumulation of copper in the liver, and manifestations of WD 

13.  1:100 people are heterozygotes for the WD mutation, WD prevalence is 1:30,000. 

14.  Treatment of WD

            a.  penicillamine is the treatment of choice, improvement is noticeable only after

6-8 months of therapy.

            b.  urinary copper excretion can be used to monitor treatment efficacy.

            c.  trientine and tetrahiomolybdate are alternative drugs for patients intolerant to

penicillamine

            d.  siderobalstic anemia due to copper deficiency is a possible complication

            e.  zinc’s mechanism of action is to inhibit copper absorption in the GI tract

            f.  liver transplantation will restore normal copper homeostasis and reverse

neurologic damage.

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