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Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Background & Aims

Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD.

Methods

In 56 patients with WD (29 men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5 ± 12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1β, IL-2, IL-6, IL-10, and TNF-α) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals.

Results

WD patients had a significantly lower TAC (p < 0.00001), lower IL-10 levels (p = 0.039), as well as both higher IL-1β (p = 0.019) and IL-6 (p = 0.005) levels compared to the control subjects. TNF-α, hs-CRP, and IL-2 did not differ from the controls. Patients with the neurological form of WD had a significantly lower TAC than those with the hepatic form (p < 0.001). In addition, the lower TAC was associated with the severity of the neurological symptoms (p = 0.02). No relationship between the inflammatory parameters and clinical symptoms was found.

Conclusions

Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients.

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Acknowledgment

The authors would like to thank Mgr. Skibova from IKEM Prague for her help with the statistical analysis.

Grant support

The study was supported by grant IGA MZ CR No. NT 12290/4 and NT 11247/4 provided by the IGA, Czech Ministry of Health.

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Authors and Affiliations

  1. First Faculty of Medicine, 4th Department of Internal Medicine, Charles University in Prague, Prague, Czech Republic

    Radan Bruha, Libor Vitek & Jaromir Petrtyl

  2. 1st Faculty of Medicine, Institute of Clinical Biochemistry and Laboratory Diagnostics, Charles University in Prague, Prague, Czech Republic

    Libor Vitek, Alena Jiraskova & Ivana Malikova

  3. Department of Internal Medicine, Central Military Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic

    Zdenek Marecek & Petr Urbanek

  4. 1st Faculty of Medicine, Pediatric Department, Laboratory for Mitochondrial Disorders, Charles University in Prague, Prague, Czech Republic

    Lenka Pospisilova & Pavel Martasek

  5. 1st Faculty of Medicine, Department of Neurology, Charles University in Prague, Prague, Czech Republic

    Sona Nevsimalova

  6. 1st Faculty of Medicine, 3rd Department of Internal Medicine, Charles University in Prague, Prague, Czech Republic

    Martin Haluzik

  7. Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

    Peter Ferenci

  8. 4th Department of Internal Medicine, General Teaching Hospital, U Nemocnice 2, 128 08, Prague 2, Czech Republic

    Radan Bruha

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  1. Radan Bruha
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Corresponding author

Correspondence to Radan Bruha.

Additional information

Communicated by: Moacir Wajner

Competing interests: None declared.

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Bruha, R., Vitek, L., Marecek, Z. et al. Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms. J Inherit Metab Dis 35, 541–548 (2012). https://doi.org/10.1007/s10545-011-9422-5

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  • DOI: https://doi.org/10.1007/s10545-011-9422-5

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