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Wilson disease





Population genetics
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Autosomal trisomies: Pathology review
Muscular dystrophies and mitochondrial myopathies: Pathology review
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Wilson disease


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High Yield Notes
27 pages

Wilson disease

9 flashcards

USMLE® Step 1 style questions USMLE

4 questions

A 30-year-old male comes to his physician for evaluation of personality changes. At work, he has recently gotten into several heated arguments with colleagues and has missed several deadlines. The patient states, “I just feel more irritable than usual, and even small things get me angry." He does not consume alcohol, tobacco, or illicit substances. Medical history is notable for a right humeral fracture that occurred 5 years ago while playing soccer. Family history is notable for “liver disease” in his maternal uncle and grandfather, but he is unaware of additional details. Physical examination reveals greenish-brown rings around the iris. The liver is palpated 4 cm below the right costal margin. Resting tremors are present in the bilateral hands. Which of the following sets of laboratory values would most likely be seen in this patient?

External References

Content Reviewers:

Rishi Desai, MD, MPH

One essential mineral that our body needs to get through the diet is copper, and typically we take in about 1 to 2 mg per day from the food we eat, things like whole grains, beans, nuts and potatoes; but really our body only needs about 0.75 mg / day, so that extra copper is excreted.

About 90% of the excess copper is excreted into the bile, where it eventually ends up as fecal copper, and the other 10% is excreted in the urine.

In Wilson disease, there’s genetic defect that results in the excess copper being kept in the body and deposited in various tissues...where it’s not supposed to be, and just like iron, free copper reacts with hydrogen peroxide in the body to form the hydroxyl radical, a reactive oxygen species that’s pretty good at damaging tissue, so over time those tissues are seriously damaged by free radical generation.

Now your liver cells, or hepatocytes, play a really important role in helping the body get rid of excess copper.

So usually the copper from the diet is absorbed in the small intestine via enterocytes, and passed off into the portal vein to the liver.

Once it’s in the liver it’s sent to a special transport protein called ATP7B, which has a couple super important jobs.

The first job, is that it binds copper to apoceruloplasmin, which is the major copper-carrying protein in the blood and is responsible for carrying 95% of the copper in blood.

After it binds copper it’s then just called ceruloplasmin, and this guy can haul 6 molecules of copper at once.

ATP7B’s other job is to gather up the rest of the copper into vesicles to be exocytosed into into the bile canaliculi, where it goes into the bile and is eventually excreted.

With Wilson disease, there’s an autosomal recessive defect in this ATP7B transport protein. As you could probably guess, that means it can’t incorporate the copper into ceruloplasmin or excrete it into the bile.

Since it’s not doing either of these things anymore, the copper builds up inside the hepatocyte and starts to produce free radicals.

Eventually, all this built up copper and free-radical damage injures or destroys the hepatocyte, causing free copper to spill out into the interstitial space and from there into the blood supply, where it’s circulated to and deposited in other tissues, where it also causes free radical damage over time.

One organ in particular is the brain, and for this reason Wilson disease can have serious neurological symptoms and complications.

Depending on where it deposits, it can cause different disorders, if it deposits in the basal ganglia, it can cause a movement disorder that’s a lot like parkinsonism.

If it gets to the cerebral cortex it can be toxic to neurons, and can lead to neuronal cell death and dementia.

Wilson's disease is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease. It is the result of inadequate copper excretion into bile and blood resulting in decreased serum ceruloplasmin, and increased copper in the urine. Copper then accumulates in the liver, brain, cornea, kidneys, joints. It is treated with chelation with penicillamine.
  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes" Journal of Medical Genetics (2007)
  6. "Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes" Journal of Medical Genetics (2007)
  7. "A practice guideline on Wilson disease" Hepatology (2003)