The non-ceruloplasmin copper test is a laboratory analysis that measures the amount of copper in the blood that is not bound to ceruloplasmin. Ceruloplasmin is a copper-carrying protein in the blood, and typically, most of the copper in the bloodstream is bound to this protein. The fraction of copper not bound to ceruloplasmin is called non-ceruloplasmin or free copper.
This test is crucial in diagnosing and managing Wilson's disease, a genetic disorder characterized by excessive copper accumulation in the body's tissues. In Wilson's disease, the function of ceruloplasmin is impaired, leading to an increase in free copper levels in the blood. Elevated non-ceruloplasmin copper levels can be toxic to the body and are typically associated with liver disease, neurological symptoms, and psychiatric disturbances.
The non-ceruloplasmin copper test is also relevant to other conditions affecting copper metabolism, including chronic liver diseases and certain neurological disorders.
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Copper, an essential trace element, is crucial for adequately functioning various metalloenzymes that support critical biological processes, including energy production and neural development. However, copper can become excessively harmful, particularly when not bound to proteins. This free copper can induce tissue damage through its pro-oxidant activity, which depletes the body's antioxidant defenses.
Typically, less than 5% of the total copper in the blood is unbound to proteins such as ceruloplasmin, making the concentration of free copper relatively low compared to total serum copper levels. As such, changes in free copper concentration might not be noticeable when only total copper levels are measured, underscoring the need for specific tests to evaluate non-ceruloplasmin copper levels.
Ceruloplasmin is the major copper-binding protein, mainly determining the total copper concentration in the serum or plasma. Nonetheless, copper is also associated with other proteins, including transcuperin, albumin, and various amino acids.
Wilson disease (WD) is a severe genetic disorder caused by mutations in the ATP7B gene, which encodes a transporter essential for copper elimination. This condition leads to excess copper in circulation and tissue accumulation. Copper overload is also linked to other health issues, including cancer, preeclampsia, and Alzheimer’s disease. The incidence of WD is approximately 1 in 30.000, and it presents primarily with hepatic or neurological symptoms. Early diagnosis is critical, as WD is treatable but can be fatal if not addressed in time.
Diagnosing WD involves a combination of laboratory and clinical tests. An ophthalmologic slit-lamp examination may reveal Kayser-Fleischer rings indicative of corneal copper deposition. Other diagnostic measures include quantifying ceruloplasmin (typically reduced in WD), 24-hour urine copper (generally elevated in WD), and liver copper content (usually increased in WD). Although genetic testing can identify mutations in ATP7B, it's only conclusive if it detects the specific mutations causing the disease in the patient, given the wide variety of possible mutations.
Since free copper is the most toxic form, measuring unbound copper in circulation directly assesses potentially harmful copper levels.
