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

Abstract

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...

Neurological features and management of Wilson disease in children: an evaluation of 12 cases

“…Presence of KF ring on opthalmologic examination or detection of mutations in the ATP7B gene support the diagnosis. The diagnosis is based on laboratory findings including reduced serum ceruloplasmin level in association with increased 24-hour urine copper, serum free copper and hepatic tissue copper (2,5). Low copper diet, D-penicillamine, triethylentetramine, amonium tetratiomolibdate and zinc are used in treatment (2)(3)(4).…”

Clinical presentation and mutations in Danish patients with Wilson disease

“…However, the diagnosis is still being challenged, and the significance attributed to the different tests is under debate. 1,9,10 The ultimate confirmation of a WND diagnosis lies in the identification of the disease-causing mutations. More than 500 mutations have been described (http://www.wilsondisease.med.…”

Clinical and genetic analysis of pediatric patients with Wilson disease

“…Both findings are reversible with medical therapy or after liver transplantation. It should be pointed out that KF rings, although very specific for WD, are rarely described in early pediatric ages and in WD children presenting with clinically asymptomatic hypertransaminasemia (8), being more frequent (up to about 50% of cases) in adolescents and young adults with more severe liver disease and/or with neurologic symptoms (9).…”