Wilson's disease in children: 37-Year experience and revised King's score for liver transplantation

Abstract

Wilson's disease (WD) is a rare liver-based disorder of copper metabolism. Prognostic criteria described by our group in 1986 to predict death without transplantation have not been universally validated. The clinical features of 88 children were reviewed, retrospectively in 74 and prospectively in 14. Data from the retrospectively recruited patients that died or survived on long-term chelation were used to evaluate the validity of our old scoring system and to devise a new prognostic index, then assessed in the 14 prospectively recruited patients. Using the old scoring system, 5 children scoring > 7, the cutoff value for death without transplantation, survived, whereas 4 scoring < 7 died (sensitivity 87% and specificity 90%). A new index based on serum bilirubin, international normalized ratio, aspartate aminotransferase (AST), and white cell count (WCC) at presentation identified a cutoff score of 11 for death and proved to be 93% sensitive and 98% specific, with a positive predictive value of 88%. When the new index was evaluated prospectively in 14 patients, it predicted the need for transplantation in only the 4 who required it, although 1 child with a score of 11 survived on medical treatment. In conclusion, the new Wilson Index is more sensitive and specific in predicting mortality without transplantation than the old scoring system, but needs to be validated in a larger number of patients. (Liver Transpl 2005;11:441-448.)

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

“…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. The fact that urinary copper levels are lower in very young children suggests an accumulation of the metal over time.…”

“…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.…”

“…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.…”

“…The diagnosis of WD was initially established with at least two of the following features: a low plasma ceruloplasmin level (<20 mg/dL), an increased basal urinary copper level (>100 lg/24 hours), an increased urinary copper level after the penicillamine challenge test (PCT; >1575 lg/24 hours), an increased liver copper level (>250 lg/g of dry weight), a positive family history, the presence of KayserFleischer (KF) rings, and Coombs' negative hemolytic anemia. 3 Furthermore, genetic testing results, when available, were considered.…”

“…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][4][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.…”