Ceruloplasmin

Ceruloplasmin Definition

Ceruloplasmin is an enzyme produced in the liver that transports more than 95% of the copper in blood plasma. Its function is to oxidize ferrous iron into ferric iron — a reaction that requires copper — in order to allow the transport of iron. The ceruloplasmin test, which assesses the levels of ceruloplasmin in the blood, is employed to diagnose a rare disease in humans known as Wilson disease, which is characterized by low levels of ceruloplasmin and very high levels of copper in several organs including the liver and the brain, and by symptoms such as nausea, changes in behavior and motor abilities, fatigue and yellowing of the skin and eyes.

Ceruloplasmin Test

The ceruloplasmin test is done usually together with other blood and urine tests to diagnose a rare inherited disorder known as Wilson disease or hepatolenticular degeneration. People with this disease experience loss of appetite, anemia, drooling, nausea, skin rash or yellowing of the skin and eyes, abdominal pain, nausea, tremors, difficulty executing certain movements, and other changes in behavior. The ceruloplasmin test is usually requested by the physician together with other urine and blood copper tests. Wilson disease is normally diagnosed when the tests show low levels of blood ceruloplasmin and high levels of copper in the urine.

Reference Range of Ceruloplasmin

The ceruloplasmin test is a blood test that determines the levels of ceruloplasmin in the blood. As with numerous clinical analyses, the levels of ceruloplasmin in the blood have been well investigated and a reference range has been established to determine whether they fall within normal values. The normal values, or reference range, for ceruloplasmin in the blood are between 20 and 50 mg/dL.

Low Levels of Ceruloplasmin

If the ceruloplasmin test reveals levels below the reference range, it is possible that the person suffers from Wilson disease. There are other conditions, however, that also decrease the levels of ceruloplasmin in the blood, most of them involving damage to the liver. Some examples include cirrhosis (when scar tissue replaces healthy tissue in the liver), liver failure and liver diseases. In addition to liver issues, low levels of blood ceruloplasmin may also indicate the presence of nephrotic syndrome, Menkes disease, aceruloplasminemia or gastrointestinal problems. This test is nevertheless usually not used to diagnose these disorders.

High Levels of Ceruloplasmin

If the ceruloplasmin test reveals levels above the reference range, it is possible that the person suffers from lymphoma (cancer in the immune system), rheumatoid arthritis, inflammation or a severe infection. Pregnant, healthy women and people who take certain medications or hormonal drugs (e.g. contraceptives or estrogen) can also show high values ceruloplasmin in the blood.

Ceruloplasmin Function

Ceruloplasmin is a multi-copper serum ferroxidase that needs copper to oxidize ferrous iron (Fe2+) into ferric iron (Fe3+) to enable cellular iron transport. Ferrous iron is taken at the cell surface, it is oxidized by ceruloplasmin and it is then transported by transferrin, which is an extracellular iron transporter that can carry iron only in its ferric form (Fe3+).

Since the production of ceruloplasmin depends on the availability of copper, copper deficiency leads to a reduction in circulating ceruloplasmin, which in turn results in the accumulation of iron in the liver and in other organs and tissues. Iron is consequently not delivered to the cells in the body when there is not enough ceruloplasmin available to oxidize iron.

In the past few years, research has unveiled the role of iron in early neurodevelopment and in neurodegneration. Since ceruloplasmin is involved in iron homeostasis, multiple disorders such as Alzheimer’s disease, Parkinson’s disease and early cognitive developmental disorders have been associated with abnormalities in ceruloplasmin production, metabolism and activity.

Quiz

1. What could low levels of blood ceruloplasmin indicate?
A. Lymphoma, rheumatoid arthritis or inflammation.
B. Wilson disease, lymphoma or Alzheimer’s disease.
C. Rheumatoid arthritis, severe infection or pregnancy.
D. Wilson disease, Menkes disease or aceruloplasminemia.

Answer to Question #1
D is correct. A ceruloplasmin test showing that the levels of blood ceruloplasmin are below the reference range could indicate the presence of Wilson disease, Menkes disease or aceruloplasminemia.

2. What are the consequences of copper deficiency?
A. A reduction in circulating ceruloplasmin and the accumulation of iron in the liver and other organs.
B. An increase in circulating ceruloplasmin and the accumulation of iron in the liver and other organs.
C. A reduction in circulating ceruloplasmin and in iron in the liver and other organs.
D. An increase in circulating ceruloplasmin and a reduction in iron in the liver and other organs.

Answer to Question #2
A is correct. Copper deficiency results in a decreased production of ceruloplasmin and a consequent reduction of circulating ceruloplasmin, which leads to the accumulation of iron in the liver and other organs because iron is not oxidized by ceruloplasmin, a step needed for iron to be transported to other parts of the body.

References

  • Ayton, S., Lei, P., Duce, J.A., Wong, B.X., Sedjahtera, A., Adlard, P.A., Bush, A.I. & Finkelstein, D.I. (2013). Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease. Annals of Neurology, 73, 4:554-9.
  • Hellman, N.E. & Gitlin, J.D. (2002). Ceruloplasmin metabolism and function. Annual Review of Nutrition, 22, 439-458.
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