Tórsdóttir et al 500 450 400 350 300 250 SOD1 activity in erythrocytes SOD-525 units Heterozygotes Controls Figure 1 Distribution of individual values of SOD1 activity in heterozygotes and controls (SOD-525 units in erythrocytes).The central box represents the values from the 25th to the 75th percentile (314–414 in heterozygotes and 289–368 in the controls).The middle line represents the median in the patients and the controls (354 and 325), respectively.The horizontal lines represent the lowest and highest value, (265 and 476) in heterozygotes, (250 and 437) in controls. Abbreviation: SOD1, Cu-Zn superoxide dismutase. different between the heterozygotes compared with controls. Still, it was possible to see a trend toward lower CP oxidative activity in the heterozygotes. As described in the Introduction, Cox and colleagues showed that after an oral and intravenous dose of labelled copper (64Cu and 67Cu), the incorporation rates into CP were slower in het- erozygotes than in normal controls but faster than in the homozygotes for WD.4 In a study by Gollan and colleagues, lowered CP-speciﬁc oxidative activity was encountered in two families with WD, in both the patients (homozygotes) and the heterozygotes, while this was not the case in other WD families studied by these authors.13 This reﬂects that the quality of CP can vary between different families with WD (reﬂecting different mutations of the ATP7B). The results of our study (although not signiﬁcant) point toward lesser quality of the CP in the heterozygotes in the Icelan- dic families with WD compared with individuals with no family history of WD. The Icelandic heterozygotes did not show any symptoms in either the liver or the nervous system, indicating that a slightly deranged copper metabolism does not promote 58 disease. Still, there are reports of mild movement disorders in heterozygotes for WD.14–17 As CP concentration and oxidative activity have been found to be signiﬁcantly lower in Alzheimer disease and Parkinson disease,18–20 the question arises whether the heterozygotic relatives of the WD patients are more likely to develop these neurodegenerative diseases compared with the general population, as they get older. In that context, the division of the heterozygotes and their con- trols into age groups would have been of interest, but this was not considered meaningful in this study as the sample was very small. Our earlier studies have not shown a correlation between the CP concentration or activity in serum or SOD1 activity in erythrocytes and age in healthy individuals,19,20 which is in accordance with other authors.21,22 SOD1 activity in erythrocytes was not signiﬁcantly different between the heterozygotes and the controls (P = 0.066), but there was a trend toward higher SOD1 activity in the heterozy- gotes (Figure 1). The trend toward higher SOD1 activity in the heterozygotes in the present study can reﬂect a slight tendency to lower copper excretion and thus higher intracellular copper in the heterozygotes compared with controls. Neuropsychiatric Disease and Treatment 2009:5