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Background and purpose The severity of Wilson's disease ( WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (Cu EXC) 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. Cu EXC 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 Cu EXC values than those with the hepatic form ( P < 0.0001). The overall ability of Cu EXC 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, Cu EXC 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. [ABSTRACT FROM AUTHOR]

In a recent meta-analysis by Ventriglia and colleagues studying the association of zinc levels with Alzheimer's disease (AD), serum zinc has been found significantly decreased in AD patients compared with healthy controls. However, such a finding does not necessarily propose the causal role of low zinc in the pathophysiology of this neurodegenerative disease. On the basis of available evidence, free copper toxicosis may play a causal role in age-related AD, and zinc therapy can be a rational causal treatment. Nevertheless, a randomized controlled clinical trial testing a definite hypothesis is needed before conclusions can be drawn about the value of zinc supplements in the treatment of AD. [ABSTRACT FROM AUTHOR]

Abstract: Wilson's disease (WD) is an inherited disorder of copper metabolism with main hepatic and neurological symptoms. Multiple sclerosis (MS) is an autoimmune and inflammatory demyelinating disease. We present two patients with coexisting WD and MS. In both cases the diagnosis of MS preceded diagnosis of WD. Both patients exhibited neurological signs typical of MS (internuclear palsy, optic neuritis). The first one displayed typical signs of WD (hypomimia, sialorrhea, behavioral changes). The second patient had liver injury without any neurological symptoms. In both cases clinical course of MS was very mild (17 and 12 years of observation) which may be caused by immunosuppressive effect of free copper. [Copyright &y& Elsevier]

The knowledge of copper (Cu) distribution in blood contributes to a better understanding of copper metabolism and to a better approach and follow up of related diseases such as Wilson’s disease (WD). Many tests can be used to investigate patients who may have WD but they show many drawbacks and do not allow real patient monitoring. Knowing that the Cu overload can result from the free and easily exchangeable form of copper in plasma, a two-step method (ultrafiltration–determination by ETAAS) was carried out to determine these two fractions. The ultrafiltration procedure and the instrumental determination showed good repeatability, and a very low limit of detection was obtained (0.7 nmol/L). In vitro stability of both ultrafiltrable copper (CuUF) and exchangeable copper (CuEXC) was studied. Plasma was ultrafiltered in 44 presumably healthy subjects to determine CuUF and CuEXC and to set reference values ranges. The method was applied on a few patients showing good correlation between both parameters and the clinical and biological features of the patients. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]