Copper speciation and total essential trace element levels in Wilson’s disease

Wilson’s disease (WD) is a rare genetic disorder characterized by copper (Cu) accumulation in the liver, brain, eyes, and kidneys due to a defective ATP7B gene. The disease is typically diagnosed through laboratory tests, including reduced ceruloplasmin (Cp) levels, increased serum free Cu, and elevated urine Cu levels. Treatment includes a low-Cu diet, drug therapy, or liver transplantation.

Figure: Structure of ceruloplasmin,  the major copper-containing  protein in blood plasma

Essential trace elements, including Cr, Mn, Fe, Co, Cu, Zn, Se, and Mo, are vital for human health. Their alteration can lead to deficiency or toxicity. In WD, the role of these elements remains partially investigated. Inductively coupled plasma mass spectrometry (ICP-MS) is commonly used to determine the total concentration of trace elements in clinical samples. However, speciation analysis is increasingly gaining attention for a more comprehensive insight into changes in the body.

This study aimed to compare the total levels of essential trace elements in plasma and urine samples of WD-treated patients and healthy controls using ICP-MS, and to conduct Cu speciation in plasma samples using HPLC-ICP-MS. The study also considered differences in elemental profiles and major Cu species depending on drug therapy.

The study enrolled 32 WD patients and 21 healthy controls. Plasma and urine samples were collected and analyzed using ICP-MS for total element concentrations and HPLC-ICP-MS for Cu speciation. The study considered three major Cu species: Cu-ceruloplasmin (Cu-Cp), Cu-human serum albumin (Cu-HSA), and Cu-low molecular mass (Cu-LMM).

In plasma, cases had lower levels of Cu (about 2.3 times), but higher levels of Zn (1.8 times) and Se (1.4 times) (p <0.001 for all). In urine, the cases had about 13 times higher levels of Cu and about 2.3 times higher levels of Zn, while the levels of Se, Co, and Mo were lower. Compared with chelating agent therapy, ZnSO4 therapy led to higher plasma Zn and Se levels and higher urine Zn levels, while chelating agent therapy caused slightly higher urine Cu levels.

Drug therapy altered/reduced the levels of Cu species, primarily the Cu-HSA and Cu-LMM fractions, offering opportunities for potential circulating biomarkers of WD. Correlations between elements suggested synergistic or antagonistic interactions occur in patients’ body fluids, which could open up a new field of research into WD.

The study's limitations include the small number of subjects, the lack of full matching for sex and age, and the absence of renal clearance data. Longitudinal studies and studies with large numbers of patients on different therapies would provide more reliable information on the levels of essential trace elements in WD and further details regarding Cu speciation analysis.

This study provides insight into the levels of essential trace elements in the plasma and urine of WD-treated cases, the impact of drug therapy for WD on the alteration of specific trace elements and three major species of Cu, potential new biomarkers, and implications for careful monitoring of drug therapy in patients with WD. Further research is needed to confirm or refute the potential of Cu-HSA and Cu-LMM as biomarkers in the diagnosis and monitoring of WD progression.

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Labtests Online: Ceruloplasmin
 WilsonDisease.org: New Guidance for Diagnosis, Treatment and Management of Wilson Disease 

 Wilson Disease Association: Lab Tracker - Copper Calculator

 Wilson Disease Association: About Wilson Disease

last time modified: July 3, 2025