Trace Element: Copper (SAAS)
Biochemistry Overview / Directory
Purpose of the test
Copper is now well established as an essential trace element. The majority of copper in the circulation is bound to caeruloplasmin which is synthesised in the liver, and binds 6-8 atoms of copper per molecule. Caeruloplasmin is an acute phase protein and can increase greatly in response to infection, injury, chronic inflammatory conditions or steroid hormones (including pregnancy, the OC pill and HRT). Copper deficiency presents as a microcytic hypochromic anaemia with marked neutropenia. Frank dietary copper deficiency is uncommon but subclinical copper deficiency may be more widespread than was first thought. The rare sex linked recessive disorder, Menke's "steely hair" disease, is characterised by a failure of intestinal copper absorption due to a defect in the gene coding for the intestinal copper transporter ATP7A. Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder due to defects in the gene coding for the copper transporter (ATP7B) in other cells. Copper accumulates in the liver and other tissues, especially the brain. Children and adolescents presenting with a variety of hepatic symptoms often associated with a normocytic anaemia should be investigated for Wilson disease. The classical presentation in adults is of progressive neurological symptoms and characteristic copper deposits in the corneas (Kayser-Fleischer rings). Chronic poisoning with copper or inherited disorder (Wilson's), leads to gross hepatic copper overload with severe liver disease in young children. Indian childhood cirrhosis has been ascribed to storage of drinking water/milk in copper vessels and there have been several cases of copper poisoning from well water.
Depending on the stage of Wilson disease at presentation, plasma copper and caeruloplasmin may be normal and can even be increased in fulminant hepatic failure. Very low plasma copper and caeruloplasmin concentrations are strongly suggestive of Wilson disease, providing the patient is not taking high doses of zinc which competes for absorption in the intestine. Measurement of the liver copper content, or of the urinary output of copper before and after challenge with the metal chelator, penicillamine, may be necessary for diagnosis. Penicillamine challenge has a high discriminatory power for distinguishing Wilson disease from hepatic copper accumulation associated with other liver diseases. Over 90 different mutations in the ATP7B gene have been found : genetic diagnosis thus often requires sequencing of the whole gene.
Reference Range
Plasma/serum copper 12-25 µmol/L.
Urine copper < 0.9 µmol/24h. Values greater than 25 µmol/24h following penicillamine are almost invariably associated with Wilson disease.
Tissue copper < 50 µg/g dry wt. Values above 250 µg/g are typical in Wilson disease
Sample Requirements
Serum (500 µL).
Urine (5 mL + 24h urine volume)
Protocols for penicillamine challenge tests and for handling liver biopsies for hepatic copper are available on request.
Storage and Transport
Stable at 4°C for weeks. Send by overnight first class post
PDF Request Form
Download Trace Element: Copper (SAAS) Request Form
Turnaround Time
1 - 2 weeks
Price
Price available on application - please contact adrianturner1@nhs.net. Discounts could be available for significant workloads.
Contacts
Dr Kishor Raja
T: 020 3299 4127
References
Raja KB, Hazary VK, Peters TJ, Warnakulasuriya S. (2006) Effect of areca nut on salivary copper concentration in chronic chewers. Biometals (In press)
