Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson’s disease in children

Müller, Thomas; Koppikar, S.V.; Taylor, Rachel; Carragher, Fiona; Schlenck, Barbara; Heinz‐Erian, Peter; Kronenberg, Florian; Ferenci, Péter; Tanner, Stuart; Siebert, Uwe; Staudinger, Roland; Mieli‐Vergani, Giorgina; Dhawan, Anil

doi:10.1016/j.jhep.2007.03.011

Cited by 102 publications

(60 citation statements)

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“…The present study has highlighted different peculiarities of these patients with respect to WD children reported elsewhere. [6][7][8][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 not always indicative of a copper storage disorder because both heterozygotes for WD and patients with other disorders may share this feature.…”

Section: Discussionmentioning

confidence: 92%

“…3,[6][7][8][9]13 In fact, all the WD patients evaluated 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.…”

Section: Discussionmentioning

confidence: 98%

“…7,26,27 As for the pediatric series, urinary copper levels have exceeded 100 lg/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 lg/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 lg/ 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.…”

Section: Discussionmentioning

confidence: 99%

“…3,9 There is only one report showing a specificity of 93% at the proposed cutoff of 1575 lg/24 hours. 9 In this study, however, the group of asymptomatic children was small (only 13 patients) and was not well characterized with respect to liver enzymes. Our study provides further and stronger evidence that PCT should not be performed in children without symptomatic liver disease regardless of the presence of neurological symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…Neurological symptoms are more frequent in adolescents and young adults [6][7][8] and are found in only 4% to 6% of pediatric cases with hepatic onset. 4,5,9 If WD is not recognized and adequately treated, the progression of hepatic and neurological damage can be very rapid, and fulminant liver failure can occur. Therefore, the prompt detection of this condition is vital.…”

mentioning

confidence: 99%

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Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease

et al. 2010

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The diagnosis of Wilson disease (WD) is challenging, especially in children. Early detection is desirable in order to avoid dramatic disease progression. The aim of our study was to re-evaluate in WD children with mild liver disease the conventional diagnostic criteria and the WD scoring system proposed by an international consensus in 2001. Forty children with WD (26 boys and 14 girls, age range 5 1.1-20.9 years) and 58 age-matched and sex-matched patients with a liver disease other than WD were evaluated. Both groups were symptom-free and had elevated aminotransferases as predominant signs of liver disease. In all WD patients, the diagnosis was supported by molecular analysis, the liver copper content, or both. A receiver operating characteristic (ROC) analysis of ceruloplasmin at the cutoff value of 20 mg/dL showed a sensitivity of 95% [95% confidence interval (CI) 5 83%-99.4%] and a specificity of 84.5% (95% CI 5 72.6%-92.6%). The optimal basal urinary copper diagnostic cutoff value was found to be 40 lg/24 hours (sensitivity 5 78.9%, 95% CI 5 62.7%-90.4%; specificity 5 87.9%, 95% CI 5 76.7%-95%). Urinary copper values after penicillamine challenge did not significantly differ between WD patients and control subjects, and the ROC analysis showed a sensitivity of only 12%. The WD scoring system was proved to have positive and negative predictive values of 93% and 91.6%, respectively. Conclusion: Urinary copper excretion greater than 40 lg/24 hours is suggestive of WD in asymptomatic children, whereas the penicillamine challenge test does not have a diagnostic role in this subset of patients. The WD scoring system provides good diagnostic accuracy. (HEPATOLOGY 2010;52:1948-1956 See Editorial on Page 1872 W ilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in a gene [ATPase, Cuþþ transporting, beta polypeptide (ATP7B)] encoding a copper-transporting, P-type ATPase.1 This disease leads to progressive copper accumulation in the liver and subsequent deposition in other organs, such as the nervous system, corneas, kidneys, bones, and joints. The distribution of the metal in diverse organs over time accounts for the wide range of clinical manifestations. 2 In the pediatric age bracket, most cases have a hepatic presentation. In the available series, the percentage of WD children presenting with isolated elevated serum aminotransferases ranges from 14% to 88%; this depends on the health policy and the type of health care provided.3-5 However, there is evidence that alterations in liver function tests may precede the onset of symptoms for a considerable time. Neurological symptoms are more frequent in adolescents and young adults [6][7][8] and are found in only 4% to 6% of pediatric cases with hepatic onset. 4,5,9 If WD is not recognized and adequately treated, the progression of hepatic and neurological damage can be very rapid, and fulminant liver failure can occur. Therefore, the prompt detection of this condition is vital. Unfortunately, the diagnosis of WD is an especi...

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Section: Discussionmentioning

confidence: 92%