Serum Copper Test: Wilson's Disease and Deficiency

Copper, an essential trace mineral, plays a pivotal role in numerous physiological processes vital for human health. While often overlooked, maintaining optimal copper levels is crucial, as both deficiency and excess can lead to severe health consequences. The serum copper test is a key diagnostic tool employed by clinicians to assess an individual's copper status, particularly in the context of suspected Wilson's disease or copper deficiency. This comprehensive article delves into the critical functions of copper, the interpretation of serum copper tests, the implications of imbalance, and practical advice on dietary sources, bioavailability, and supplementation.

The Vital Role of Copper in Human Health

Copper is an indispensable micronutrient that functions primarily as a cofactor for numerous metalloenzymes involved in a wide array of metabolic pathways. Its unique ability to cycle between cuprous (Cu+) and cupric (Cu2+) states allows it to participate in electron transfer reactions, making it critical for energy production and antioxidant defense.

Key Functions of Copper:

• Energy Production: Copper is an essential component of cytochrome c oxidase, the terminal enzyme in the electron transport chain, crucial for aerobic respiration and ATP synthesis.
• Connective Tissue Formation: It is a cofactor for lysyl oxidase, an enzyme required for the cross-linking of collagen and elastin, vital for the integrity of bones, cartilage, skin, and blood vessels.
• Iron Metabolism: Copper is intricately linked with iron metabolism. It is required for the proper functioning of ceruloplasmin, a ferroxidase enzyme that oxidizes ferrous iron (Fe2+) to ferric iron (Fe3+), allowing it to bind to transferrin for transport throughout the body. Without adequate copper, iron cannot be properly mobilized from storage sites, leading to functional iron deficiency and anemia, even in the presence of sufficient iron stores.
• Nervous System Function: Copper is essential for the synthesis of neurotransmitters (e.g., dopamine beta-hydroxylase converts dopamine to norepinephrine), myelin formation, and overall neuronal health. Copper deficiency can lead to significant neurological dysfunction.
• Immune Function: It supports the development and function of immune cells, including lymphocytes and phagocytes, contributing to a robust immune response.
• Antioxidant Defense: Copper-zinc superoxide dismutase (Cu/Zn-SOD) is a crucial antioxidant enzyme that protects cells from oxidative damage by converting harmful superoxide radicals into less reactive species.
• Melanin Production: Copper is a cofactor for tyrosinase, an enzyme involved in the synthesis of melanin, the pigment responsible for hair, skin, and eye color.

Understanding the Serum Copper Test

The serum copper test measures the total amount of copper circulating in the blood. However, to accurately assess copper status, it is often interpreted in conjunction with other markers, primarily ceruloplasmin.

Types of Copper in Blood and Related Tests:

• Total Serum Copper: This test measures the total concentration of copper in the blood serum. The vast majority (approximately 90-95%) of copper in the blood is bound to ceruloplasmin, a copper-carrying protein synthesized in the liver. A smaller fraction is bound to albumin, and a tiny amount exists as "free" or unbound copper.
• Ceruloplasmin: This protein is not only a copper transporter but also an acute phase reactant and a ferroxidase. Measuring ceruloplasmin levels provides insight into the body's capacity to transport copper and is a critical marker for diagnosing Wilson's disease and certain copper deficiencies.
• Free Copper: This refers to the small fraction of copper not bound to ceruloplasmin. It is calculated by subtracting the copper bound to ceruloplasmin (ceruloplasmin level x 3 µg copper/mg ceruloplasmin) from the total serum copper. Elevated free copper is a hallmark of Wilson's disease, as the body's ability to incorporate copper into ceruloplasmin and excrete it is impaired, leading to toxic accumulation of unbound copper.

Interpretation of Results:

• Low Serum Copper and Low Ceruloplasmin: Often indicates copper deficiency.
• Low Serum Copper and Very Low Ceruloplasmin with High Free Copper: Highly suggestive of Wilson's disease.
• High Serum Copper and High Ceruloplasmin: Can be seen in conditions like inflammation, infections, pregnancy, or with oral contraceptive use, as ceruloplasmin is an acute phase reactant. It does not necessarily indicate copper toxicity.
• High Serum Copper with Normal/Low Ceruloplasmin and High Free Copper: Can indicate acute copper toxicity, but this is less common than Wilson's disease.

Serum Copper Reference Ranges

It is important to note that normal ranges can vary slightly between different laboratories due to variations in testing methodologies and populations. Always refer to the specific reference ranges provided by the laboratory performing the test.

| Population | Normal Range | Units | Notes