R A P I D C O M M U N I C A T I O N Ceruloplasmin and superoxide dismutase (SOD1) in heterozygotes for Wilson disease: A case control study Gudlaug Tórsdóttir1,2 Grétar Gudmundsson3 Jakob Kristinsson1 Jón Snaedal2 Torkell Jóhannesson1 1Institute of Pharmacy, Pharmacology and Toxicology, Department of Pharmacology and Toxicology, University of Iceland, Reykjavík, Iceland; 2Department of Geriatrics; 3Department of Neurology, Landspítali – University Hospital, Reykjavík, Iceland Correspondence: Gudlaug Tórsdóttir Institute of Pharmacy, Pharmacology and Toxicology, Department of Pharmacology and Toxicology, University of Iceland, Hofsvallagata 53, 107 Reykjavík, Iceland Tel +354 525 5130 Fax +354 525 5140 Email gudlaugt@hi.is Abstract: At the time of this study, there were ﬁve known patients with Wilson disease (WD) in Iceland. The mutation, a 7-bp deletion in exon 7 on chromosome 13 for WD, is only known in Iceland. In twenty healthy Icelandic heterozygotes for WD and their age- and gender-matched controls, copper concentration in plasma, ceruloplasmin (CP) concentration, CP oxidative activity and CP-speciﬁc oxidative activity in serum and superoxide dismutase (SOD1) activity in erythrocytes were determined. The same determinations were done on the ﬁve WD patients. There was no signiﬁcant difference in these parameters between the heterozygotes and the controls, although an inclination toward lower CP determinations and higher SOD1 activity in the heterozygotes was noted. As expected the WD patients were low on the copper and CP parameters, but their SOD1 activity was within the upper normal range. In conclusion, the CP parameters and SOD1 activity are within the normal range in Icelandic heterozygotes for WD, although with a trend toward mild dyshomeostasis. This may indicate subclinical copper reten- tion in the heterozygotes, but a bigger study group is needed to conﬁrm this. Keywords: ceruloplasmin, SOD1, heterozygotes, Wilson disease Introduction Wilson disease (WD) is characterized by decreased biliary copper excretion and reduced incorporation of copper in apoceruloplasmin, resulting in lower levels of ceruloplasmin (CP) and copper in serum but copper accumulation in various organs and tissues. WD is an autosomal recessive disease of copper transport, and the gene for WD has been mapped to the short arm of chromosome 13.1 It was cloned and coded for as a putative copper transporting P-type ATPase (ATP7B).2,3 WD may present under a variety of clini- cal symptoms, most commonly from liver and/or as neuropsychiatric disturbances. The incidence of hypoceruloplasminemia in heterozygotes for WD is not known, but they usually have a normal CP concentration in serum, although it may be slightly reduced.4,5 The heterozygotes are most commonly clinically asymptomatic and have a normal copper concentration in serum. They may however, show some signs of disturbed copper metabolism. While patients with WD do not incorporate radioactive copper (64Cu and 67Cu) into CP, the heterozygotes incorporate the isotopes into CP at a rate between that of normal individuals and WD patients.4 Cu-Zn superoxide dismutase (SOD1) activity in erythrocytes is known to be lowered in copper deﬁciency, but the correlation with copper and CP in serum is poor.6 Copper-chelating treatment has been found to lower SOD1 activity in erythrocytes, and it was concluded that the SOD1 activity in erythrocytes reﬂects the availability of intracellular copper.6 SOD1 activity was found to be the same in three untreated WD patients, compared with controls, but was lowered after treatment with D-penicillamine.7 To our knowledge no study has been done on SOD1 in heterozygotes for WD. Neuropsychiatric Disease and Treatment 2009:5 55–59 © 2009 Tórsdóttir et al, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 55