A 30-year-old male with cirrhosis, dementia, and Parkinson-like symptoms is diagnosed with a hereditary metabolic disease resulting from the accumulation of a certain metal in various tissues. Impairment of which of the following elimination pathways is most likely responsible?
1.Secretion into bile
2.loop of henle secretion into lumen of kidney
3.Glomerular filtration
4.Bleeding
5.Duodenal secretion
Summary
This patient is suffering from Wilson disease, a disorder that results from copper deposition in various tissues.
The main route of copper elimination, and that impaired in Wilson disease, is via hepatocyte-mediated secretion of copper into the bile.
In Wilson disease, also known as hepatolenticular degeneration, a defect in the ATP7B gene product, P-type copper ATPase, leads to impaired copper trafficking and secretion into the bile. This results in copper accumulation within liver cells and the eventual release of free copper into circulation. Free copper generates free radicals that damage tissues.
Heidelbaugh and Bruderly discuss the diagnostic evaluation of patients with cirrhosis and chronic liver failure. If one suspects Wilson disease (usually in a patient younger than 40 years with family history of liver disease), serum ceruloplasmin and copper levels should be measured. However, the authors note that screening all patients with chronic hepatic injury for Wilson disease is not indicated.
Treatment for Wilson disease consists of a low-copper diet and lifelong copper chelating agents. Wiggelinkhuizen et al. conducted a systematic review of 1 randomized trial and 12 observational studies evaluating D-penicillamine, trientine, tetrathiomolybdate, or zinc monotherapy as initial treatment for Wilson disease. The authors concluded that insufficient evidence existed to determine relative treatment effects of the various drugs.
Illustration A depicts copper metabolism in patients with Wilson disease. Note that there is reduced excretion and, thus, retention of copper.
Illustration B shows an histology image of hepatocytes in Wilson’s disease. The rhodadine stain highlights the copper deposition.