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

• Published in: Journal of inherited metabolic disease Vol. 35; no. 3; pp. 541 - 548
• Main Authors: Bruha, Radan, Vitek, Libor, Marecek, Zdenek, Pospisilova, Lenka, Nevsimalova, Sona, Martasek, Pavel, Petrtyl, Jaromir, Urbanek, Petr, Jiraskova, Alena, Malikova, Ivana, Haluzik, Martin, Ferenci, Peter
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.05.2012; Springer; Blackwell Publishing Ltd
• Subjects: Adenosine Triphosphatases - genetics; Adult; Age; Antioxidants; Antioxidants - metabolism; ATP7B gene; Biochemistry; Biological and medical sciences; Cation Transport Proteins - genetics; Copper; Copper - metabolism; Copper-transporting ATPases; Data processing; Disposition; Female; Genetic Predisposition to Disease; Hepatolenticular Degeneration - blood; Hereditary diseases; Human Genetics; Humans; Inflammation; Interleukin 1; Interleukin 10; Interleukin 2; Interleukin 6; Interleukin-10 - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Internal Medicine; Liver; Male; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metals (hemochromatosis...); Middle Aged; Mutation; Nervous System Diseases - blood; Original Article; Other metabolic disorders; Oxidative Stress; Pediatrics; Point mutation; Tumor necrosis factor- alpha; Wilson's disease; Phenotypic Manifestation; Amyotrophic Lateral Sclerosis; Wilson Disease; ATP7B Gene; Chain Breaking Antioxidant; Human; Biological fluid; Nervous system diseases; Wilson disease; Nutrition; Patient; Metabolic diseases; Antioxidant; Enzymopathy; Genetic disease; Association; Capacity; Digestive diseases; Genetics; Serum; Copper
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-011-9422-5

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.