Exchangeable copper: a reflection of the neurological severity in Wilson's disease

Eur J Neurol. 2017 Jan;24(1):154-160. doi: 10.1111/ene.13171. Epub 2016 Oct 14.

Abstract

Background and purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Wilson's disease; brain; copper chelators; exchangeable copper; free copper; liver; neurological disorders; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Brain / diagnostic imaging*
  • Copper / metabolism*
  • Female
  • Hepatolenticular Degeneration / diagnosis*
  • Hepatolenticular Degeneration / diagnostic imaging
  • Hepatolenticular Degeneration / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers
  • Copper