title: Exchangeable copper: a reflection of the neurological severity in Wilson's disease.
abstract: The severity of Wilson's disease (WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (CuEXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity.
  
  
  
  Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging (MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. CuEXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups.
  
  
  
  Extra-hepatic patients had significantly higher CuEXC values than those with the hepatic form (P < 0.0001). The overall ability of CuEXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 μmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, CuEXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score (r = 0.45, P = 0.016), the Kayser-Fleischer ring score (r = 0.46, P = 0.014) and the brain MRI score (r = 0.38, P = 0.048), but it was not correlated with the hepatic score.
  
  
  
  Exchangeable copper determination is useful when diagnosing WD as a value >2.08 μmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes.
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Neurology Department, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: A
authors.identifier: 0000-0002-5640-7534
authors.initials: A
authors.lastname: Poujois
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Neurology Department, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: J-M
authors.initials: JM
authors.lastname: Trocello
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Toxicology Laboratory, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Djebrani-Oussedik
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Toxicology Laboratory, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Poupon
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Molecular Biology and Biochemistry Department, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Collet
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Neurology Department, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Girardot-Tinant
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Hepatobiliary Centre, DHU Hepatinov, AP-HP, Paul Brousse Hospital, Villejuif, France.
authors.forename: R
authors.initials: R
authors.lastname: Sobesky
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Hepatology and Pediatrics Department, AP-HP, Kremlin-Bicètre Hospital, Kremlin-Bicètre, France.
authors.forename: D
authors.initials: D
authors.lastname: Habès
authors.affiliation: Hepatology and Pediatrics Department, AP-HP, Necker Hospital, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Debray
authors.affiliation: Hepatology and Gastroenterology Department, CHU Besancon, Besancon, France.
authors.forename: C
authors.initials: C
authors.lastname: Vanlemmens
authors.affiliation: Neurology Department, CHU Marseille, Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Fluchère
authors.affiliation: Neurology Department, CHU Toulouse, Toulouse, France.
authors.forename: F
authors.initials: F
authors.lastname: Ory-Magne
authors.affiliation: Biostatistics Unit, EA2694, CHRU Lille, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Labreuche
authors.affiliation: Mathematics Laboratory, UMR CNRS 8524, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Preda
authors.affiliation: National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.|Neurology Department, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Woimant
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging*; D003300:Copper / Q000378:metabolism*; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003300:Copper
keywords: Wilson's disease; brain; copper chelators; exchangeable copper; free copper; liver; neurological disorders; prognosis