Review Question - QID 101171

The clinical picture and treatment with penicillamine are consistent with Wilson disease. Kinky, easily breakable hair is a feature of Menkes disease, another copper transport disorder associated with growth failure, seizures, and developmental delay.

The genetic mutation responsible for Wilson disease impairs copper-trafficking within hepatocytes. This leads to copper accumulation within hepatocytes since the main routes of copper export (via bile and into the bloodstream bound with ceruloplasmin) are impaired. Eventually, this excess copper accumulates and causes tissue damage. Penicillamine, a copper chelating agent, functions by removing excess loosely-bound serum copper

Riley et al., in a review on chronic liver disease, report that Wilson disease is an important hereditary disorder to consider in the differential diagnosis of chronic liver disease. Other hereditary forms of liver disease include hemochromatosis and alpha1-antitrypsin deficiency.

Ala et al. discuss the role the P-type ATPase (product of ATP7B gene) in the transport of copper into the trans-Golgi compartment, for incorporation into the plasma protein ceruloplasmin, and into the bile, for excretion of excess stores. When this gene product does not function correctly, there is an accumulation of hepatic copper, which leads to the hepatic and neurological features of Wilson disease.

Illustration A depicts the multiple organ systems affected by Wilson disease.

Incorrect Answers:
Answer 2: Cirrhosis develops in Wilson disease due to hepatic damage from copper-generated free radicals.
Answer 3: Hemiballismus develops in Wilson disease as a result of copper deposits in the subthalamic nucleus.
Answer 4: Copper deposits in the cornea result in Kayser-Fleischer rings, a pathognomonic physical finding of Wilson disease.
Answer 5: Parkinson-like symptoms result in WIlson disease due to copper deposits in the putamen.