Format

Send to

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

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

Author information

1
National Reference Centre for Wilson's Disease, AP-HP, Lariboisière Hospital, Paris, France.
2
Neurology Department, AP-HP, Lariboisière Hospital, Paris, France.
3
Toxicology Laboratory, AP-HP, Lariboisière Hospital, Paris, France.
4
Molecular Biology and Biochemistry Department, AP-HP, Lariboisière Hospital, Paris, France.
5
Hepatobiliary Centre, DHU Hepatinov, AP-HP, Paul Brousse Hospital, Villejuif, France.
6
Hepatology and Pediatrics Department, AP-HP, Kremlin-Bicètre Hospital, Kremlin-Bicètre, France.
7
Hepatology and Pediatrics Department, AP-HP, Necker Hospital, Paris, France.
8
Hepatology and Gastroenterology Department, CHU Besancon, Besancon, France.
9
Neurology Department, CHU Marseille, Marseille, France.
10
Neurology Department, CHU Toulouse, Toulouse, France.
11
Biostatistics Unit, EA2694, CHRU Lille, Lille, France.
12
Mathematics Laboratory, UMR CNRS 8524, Lille, France.

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

PMID:
27739240
DOI:
10.1111/ene.13171
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center