When you have jaundice, fatigue, abdominal pain, behavioral changes, tremors, or other symptoms that a healthcare practitioner thinks may be due to Wilson disease or, rarely, to copper deficiency or excess; at intervals when you are being treated for a copper-related condition
A blood sample is obtained by inserting a needle into a vein and/or a 24-hour urine sample is collected. Care must be taken, especially with a 24-hour urine sample, not to contaminate the sample with an external source of copper. Talk to your healthcare practitioner and/or the laboratory that will perform the test about necessary precautions. If a urine or blood copper test result is higher than expected, your healthcare practitioner may have the test repeated with a new sample to confirm the findings. Sometimes a healthcare practitioner performs a liver biopsy.
Copper is an essential mineral that the body incorporates into enzymes. These enzymes play a role in the regulation of iron metabolism, formation of connective tissue, energy production within cells, the production of melanin (the pigment that produces skin color), and the function of the nervous system. This test measures the amount of copper in the blood, urine, or liver (hepatic).
Copper is found in many foods including nuts, chocolate, mushrooms, shellfish, whole grains, dried fruits, and liver. Drinking water may acquire copper as it flows through copper pipes, and food may acquire it when people cook or serve food in copper dishes.
- Normally, the body absorbs copper from food or liquids in the intestines, converts it to a non-toxic form by binding it to a protein, and transports it to the liver.
- The liver stores some of the copper and binds most of the rest to another protein called apoceruloplasmin to produce the enzyme ceruloplasmin. About 95% of the copper in the blood is bound to ceruloplasmin, and most of the rest is bound to other proteins such as albumin.
- Only a small amount is normally present in the blood in a free (unbound) state.
- The liver eliminates excess copper into the bile and it is removed from the body in the stool. Some copper is also eliminated in the urine.
Both excess and deficiency of copper are rare. Wilson disease, a rare inherited disorder, can lead to excess storage of copper in the eyes, liver, brain, and other organs. Copper excess (toxicity) can also occur with absorbing large amounts over a short period of time (acute exposure) or various amounts over a long period (chronic exposure).
Copper deficiency may occasionally occur in conditions associated with severe malabsorption, such as cystic fibrosis and celiac disease, and in infants exclusively fed cow-milk formulas. It can also occur in malnourished children as well as people who megadose zinc-containing vitamins.
A rare X-linked genetic condition called Menkes kinky hair syndrome leads to copper deficiency in the brain and liver of affected infants. The disease, which affects primarily males, is associated with seizures, delayed development, abnormal artery development in the brain, and unusual gray brittle kinky hair.
How is the test used?
Copper testing is primarily used to help diagnose Wilson disease, a rare inherited disorder that can lead to excess storage of copper in the liver, brain, and other organs. Less commonly, a copper test may be used to detect copper excess due to another condition, to detect a copper deficiency, or to monitor treatment for one of these conditions.
Typically, a total blood copper test is ordered along with a ceruloplasmin level. If the results from these tests are abnormal or unclear, then they may be followed by a 24-hour urine copper test to measure copper elimination and/or a copper test performed on a liver biopsy to evaluate copper storage in the liver.
Sometimes a free (unbound) blood copper test is also ordered. If Wilson disease is suspected, genetic testing may be performed to detect mutations in the ATP7B gene. However, these tests have limited availability and are usually performed in special reference or research laboratories.
Rarely, a copper test may be used to help diagnose Menkes kinky hair syndrome, a rare inherited disorder of copper transport dysfunction (see below).
When is it ordered?
One or more copper tests are ordered along with ceruloplasmin when you have signs and symptoms that a healthcare practitioner suspects may be due to Wilson disease, excess copper storage, or copper poisoning. These signs and symptoms may include:
- Nausea, abdominal pain
- Behavioral changes
- Difficulty walking
- Persistent involuntary muscle contractions that cause repetitive or twisting motions (dystonia)
- Diarrhea and vomiting
- Trouble swallowing or speaking
- Dark brown rings around the iris of the eyes (Kayser-Fleischer rings)
Testing may be ordered when you have signs and symptoms that may be due to a copper deficiency, such as:
- Abnormally low numbers of neutrophils, a type of white blood cell (neutropenia)
- Less commonly, neurologic symptoms and delayed growth in children
One or more of the copper tests may be ordered periodically when monitoring is recommended.
A hepatic (liver) copper test may be ordered to further investigate copper storage when copper and ceruloplasmin results are abnormal or equivocal.
What does the test result mean?
Copper test results must be evaluated in context and are usually compared to ceruloplasmin levels. Abnormal copper results are not diagnostic of a specific condition; they indicate the need for further investigation. Interpretation can be complicated by the fact that ceruloplasmin is an acute phase reactant – it may be elevated whenever inflammation or severe infections are present. Both ceruloplasmin and copper are also increased during pregnancy and with estrogen and oral contraceptive use.
Test results may include:
Test Wilson Disease Copper Toxicity Menkes Disease (Kinky Hair Syndrome) Copper Deficiency Copper, blood Low but may be normal High Low Low Copper, serum free High High Low Low Ceruloplasmin Low but may be normal High Low Low Copper, urine Very high High Low Low Copper, liver/hepatic* Positive but, depending on the site sampled, may be negative High or normal Low Low
*Excess copper in the liver is often unevenly distributed and may not be detected in a sample.
- Low blood copper concentrations along with increased urine copper levels, low ceruloplasmin levels, and increased hepatic copper are typically seen with Wilson disease.
- Increased blood and urine copper concentrations and normal or increased ceruloplasmin levels may indicate exposure to excess copper or may be associated with conditions that decrease copper excretion, such as chronic liver disease, or that release copper from tissues, such as acute hepatitis. Increased hepatic copper may be present with chronic conditions.
- Decreased blood and urine copper concentrations and decreased ceruloplasmin may indicate a copper deficiency.
- A normal hepatic copper test may indicate that copper metabolism is functioning properly or that the distribution of copper in the liver is uneven and the sample is not representative of the person's condition.
If you are being treated for Wilson disease or copper toxicity with drugs that bind copper (chelators), then your 24-hour urine copper levels may be high until body copper stores decrease. Eventually, blood copper and 24-hour urine copper levels should return to normal.
If you are treated for a condition related to copper deficiency and your ceruloplasmin and total copper levels rise, then the condition is likely responding to the treatment.
Can I choose either a blood (total or free) or urine copper test?
Should I be taking copper supplements or trying to get more copper in my diet?
Do I need to have a liver biopsy?
What is Menkes kinky hair syndrome?
Menkes kinky hair syndrome, also called copper transport disease, is a rare inherited disorder that causes a deficiency in copper. The syndrome is caused by mutations in the ATP7A gene located on the X chromosome. It is passed from parent to child in an X-linked recessive manner. This means that girls must inherit two copies of the mutated gene in order to be affected. Because boys only have one X chromosome, they can be affected if the mutation is present on the one X chromosome, making the condition much more common in males.
The mutation leads to uneven distribution of copper in the body. It may build up in tissues of the intestines and kidneys, for example, but may be deficient in areas such as the brain. Symptoms of the syndrome typically develop in infancy and many children die by age 3. Signs and symptoms include sparse, kinky hair, failure to grow at an expected rate and developmental delay, nervous system deterioration, weak muscle tone and seizures. The incidence of this syndrome is about 1 in 100,000 infants.
Is there anything else I should know?
Medications such as carbamazepine and phenobarbital can increase blood copper levels. They may also be elevated with rheumatoid arthritis and with some cancers and decreased with a variety of conditions associated with malabsorption, such as cystic fibrosis.
Total serum copper concentrations are normally low at birth, rise over the next few years, peak, and then decline slightly to a relatively stable level.