These patients intriguingly shared some biochemical features with WD patients. It is noteworthy that WD patients 23 and 24 (Table 2) were siblings who showed
features very similar to those of CDG patients included in the control group, but in both CDG was excluded on the basis of a normal transferrin isoelectric focusing profile. Their serum aminotransferase levels normalized after 20 or 4 months of penicillamine treatment. The features of our series are remarkably different from those of other pediatric reports, which in most cases have included WD children with either acute or chronic symptomatic liver disease or liver failure.3, 6-9, 13 In fact, all the WD patients evaluated selleckchem in the present study were referred for raised aminotransferases and could be considered asymptomatic or presymptomatic. Therefore, this population represents a valuable specimen for assessing the appropriateness of the
WD diagnostic criteria in children with mild liver disease. The present study has highlighted different peculiarities of these patients with respect to WD children reported elsewhere.6-9, 13 The measurement of ceruloplasmin serum levels is also a first-step test for the diagnosis of WD in children with mild liver disease, as demonstrated by the good sensitivity and acceptable specificity of this test at the cutoff of 20 mg/dL in the studied population. Obviously, low levels of ceruloplasmin are Staurosporine order not always indicative of a copper storage disorder because both heterozygotes for WD and patients with other disorders may share this feature.20-23 Furthermore, as click here reported elsewhere, ceruloplasmin serum levels are also influenced by the ATP7B genotype.24, 25 As for basal daily urinary copper
excretion, on the basis of our results, the diagnosis of WD should be considered when this test produces a value > 40 μg/24 hours. This cutoff value has also been recently stressed by AASLD guidelines,2 although its diagnostic accuracy has not yet been defined. There is only one report describing a sensitivity of 68% at the cutoff value of 40 μg/24 hours in an adult population.26 Among the adult series, the sensitivity of basal urinary copper excretion at the cutoff value of 100 μg/24 hours is 59% to 88%.7, 26, 27 As for the pediatric series, urinary copper levels have exceeded 100 μg/24 hours in 81% to 94% of cases.5, 9, 28 In symptomatic and asymptomatic children, the sensitivity for basal cupriuria at the cutoff value of 63.5 μg/24 hours is approximately 95% and 70%, respectively.3, 9 No data are available about the specificity of this test because the cutoff value of 40 μg/24 hours has never been evaluated; our results suggest that this is the optimal threshold both as a single test and in the context of the WD scoring system in children with mild liver disease suspected of having WD.