Wilson disease

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Wilson disease


Genetic disorders


Alagille syndrome (NORD)

Familial adenomatous polyposis

Familial hypercholesterolemia

Hereditary spherocytosis

Huntington disease

Li-Fraumeni syndrome

Marfan syndrome

Multiple endocrine neoplasia

Myotonic dystrophy


Polycystic kidney disease

Treacher Collins syndrome

Tuberous sclerosis

von Hippel-Lindau disease




Cystic fibrosis

Friedreich ataxia

Gaucher disease (NORD)

Glycogen storage disease type I

Glycogen storage disease type II (NORD)

Glycogen storage disease type III

Glycogen storage disease type IV

Glycogen storage disease type V


Krabbe disease


Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)

Niemann-Pick disease type C

Niemann-Pick disease types A and B (NORD)

Phenylketonuria (NORD)

Polycystic kidney disease

Primary ciliary dyskinesia

Sickle cell disease (NORD)

Tay-Sachs disease (NORD)

Wilson disease

Cri du chat syndrome

Williams syndrome

Angelman syndrome

Prader-Willi syndrome

Beckwith-Wiedemann syndrome

Mitochondrial myopathy

Klinefelter syndrome

Turner syndrome

Fragile X syndrome

Friedreich ataxia

Huntington disease

Myotonic dystrophy

Down syndrome (Trisomy 21)

Edwards syndrome (Trisomy 18)

Patau syndrome (Trisomy 13)

Alport syndrome

Fragile X syndrome

Fabry disease (NORD)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency


Lesch-Nyhan syndrome

Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)

Muscular dystrophy

Ornithine transcarbamylase deficiency

Wiskott-Aldrich syndrome

X-linked agammaglobulinemia

Autosomal trisomies: Pathology review

Miscellaneous genetic disorders: Pathology review

Muscular dystrophies and mitochondrial myopathies: Pathology review


Wilson disease


0 / 9 complete

USMLE® Step 1 questions

0 / 4 complete

High Yield Notes

27 pages


Wilson disease

of complete


USMLE® Step 1 style questions USMLE

of complete

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

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Wilson disease p. 404

Autosomal recessive disorders

Wilson disease p. 404

Chromosome abnormalities

Wilson disease p. 404

Cirrhosis p. 398

Wilson disease p. 404

Copper metabolism

Wilson disease p. 404

Fanconi syndrome p. 610

Wilson disease p. 404

Hemolytic anemia p. 429

Wilson disease p. 404


Wilson disease p. 404

Kayser-Fleischer rings

Wilson disease as cause p. 404

Liver failure

Wilson disease as cause p. 404


Wilson disease as cause p. 404


for Wilson disease p. 404

Renal disease

Wilson disease p. 404

Wilson disease p. 404

chromosome association p. 62

Fanconi syndrome p. 610

free radical injury and p. 213

Zinc p. 69

Wilson disease p. 404


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.


Wilson disease is a rare autosomal recessive genetic disorder that causes excessive accumulation of copper in various tissues of the body, particularly the liver, and brain as a result of a mutation in the ATP7B gene. Symptoms of Wilson disease can vary widely and may include fatigue, abdominal pain, muscle stiffness or tremors, and a characteristic brown ring around the cornea of the eye known as a Kayser-Fleischer ring. Over time, copper accumulation in the liver can lead to liver disease and cirrhosis, and copper accumulation in the brain can cause neurological symptoms such as movement disorders, psychiatric symptoms, and cognitive decline.


  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)

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