Pediatric Wilson Disease Research Articles

Efficacy and safety of D-penicillamine, trientine, and zinc in pediatric Wilson disease patients

ObjectivesWilson disease (WD) is a rare genetic disease affecting copper metabolism and the biliary tract’s copper excretion. Lifelong medication is necessary to prevent liver failure, neurological complications, and death. Although D-penicillamine (DPA), trientine, and zinc are used to treat WD, there is limited research on the long-term outcomes of these drugs, especially in children. This study aimed to evaluate the efficacy and safety of DPA, trientine, and zinc in patients diagnosed with WD during childhood.MethodsNinety out of 92 patients were included in the analysis, excluding two patients who underwent liver transplantation without drug treatment due to an acute liver failure diagnosis. Treatment outcomes and reasons for discontinuation of therapy in 148 treatment blocks (37 DPA, 50 trientine, and 61 zinc) were analyzed using Kaplan–Meier analysis.ResultsThe median age at diagnosis was 8.3 years. There was a statistically significant difference in drug changes due to treatment ineffectiveness among the three drugs: trientine (22/50, 44%), zinc (15/61, 25%), and DPA (2/37, 5%) (all p < 0.05). Regarding drug changes due to adverse effects, the rate was the highest for DPA, followed by zinc and trientine. There were significant differences between DPA and zinc, zinc and trientine (all p < 0.05), but no significant difference was observed between DPA and zinc (p = 0.22).ConclusionsIn pediatric WD, DPA, zinc, and trientine have therapeutic effects in that order. However, DPA and zinc are associated with more adverse effects compared to trientine.

Adequate Chelation and Cupriuresis in Hepatic Wilson Disease Patients Under Combination (Chelator + Zinc) Therapy at 2 Years of Follow-up

Role of 24-h urinary copper excretion (UCE) in monitoring Wilson disease (WD) on combination (chelator+Zinc) therapy is not well studied, especially in the pediatric population. Hence, the present study is conducted with an aim to evaluate UCE and its role in deciding therapeutic adequacy in pediatric WD on long-term follow-up. All WD patients <18 years of age and on combination therapy with at least one UCE available after the first year of treatment were included. Liver biochemistries, UCE, and serum non-ceruloplasmin bound copper (NCC) were assessed at diagnosis and various follow-ups. For assessment of treatment efficacy, criteria for adequate chelation (CAC) were defined as fulfillment of both (i) AST & ALT ≤1.5 times upper limit of normal, serum albumin >35gm/L, INR <1.5 and (ii) UCE <500 mcg/day. Of the 74 included children, 70 (94.5%), 45 (60.8%), 28 (37.8%) and 21 (28.3%) completed 2-, 3-, 5-, and 7-year follow-up, respectively. Liver biochemistries improved significantly within 1 year of treatment. UCE (mcg/day) decreased significantly from baseline of 654.08±803.78 to 308.23±175.93 at 2 years with no further change at 3- and 5-years follow-up. UCE (mcg/day) at 2 years was <200 in 28.5%, 200-500 in 55.7%, and >500 in 15.7%. 61% achieved CAC in 2 years. On multivariate cox regression, treatment compliance was predictor for CAC achievement (Odds ratio: 3.48, 95%CI: 1.36-8.86. P=0.009). UCE declines significantly from baseline to <500 mcg/day within 2 years. Majority of treatment-compliant patients achieve CAC within 2 years of combination therapy.

THU-262 - Genetic modifiers of liver phenotypes in pediatric Wilson disease: liver biopsy and transient elastography based study

THU-262 - Genetic modifiers of liver phenotypes in pediatric Wilson disease: liver biopsy and transient elastography based study

Is Prolonged Copper Restriction Needed in Pediatric Wilson's Disease?

Dietary copper restriction in Wilson's disease is recommended mostly for 1 year or until showing normal liver enzymes. Little is known about the effect of long-term copper restriction on copper and nutritional status in the body. The relationship between daily copper consumption and serum and urine copper parameters, liver enzymes, and dietary contents was investigated. In this study, 32 pediatric Wilson's disease patients who had been on treatment at least for 12 months were included. Clinical features, liver enzymes, serum total copper concentrations, non-ceruloplasmin bound copper concentrations, adjusted copper concentrations, 24-hour urine copper excretions, and macro- and micronutrient consumptions were analyzed. In total, 27 patients reported following copper-restricted diets, while daily copper consumption was low only in 7 patients (21.9%). Total copper concentrations and non-ceruloplasmin-bound copper concentrations were low at 78.1% and 53.1%, respectively. All but one adjusted copper concentration were within normal limits. Total copper concentrations, adjusted copper concentration, and non-ceruloplasmin-bound copper concentrations correlated with each other but none correlated with urine copper excretions. Daily copper consumption was inversely correlated with total copper concentrations (P = .041, r = -0.363) but not correlated with non-cerulo plasmin-bound copper concentrations and adjusted copper concentrations. There was no relationship between liver enzymes and daily copper consumption and serum and urine copper parameters. High fat consumption with low fiber and vitamin B6 was more common in low daily copper consumption group (P = .033, P = .029, P = .007, respectively). Daily copper consumption may be the least effective or non-effective factor on liver enzymes in Wilson's disease. Prolonged copper restriction may result in unintentional dietary imbalance. Avoidance of undernutrition and high-fat meals, as well as enrichment of the meals with vitamin B6 and fiber, should be encouraged during copper-restricted diets.

COMPREHENSIVE ANALYSIS OF THE EFFICACY OF LIVER TRANSPLANTATION IN PEDIATRIC PATIENTS WITH WILSON’S DISEASE

Background: The aim of the present study is to evaluate the results of liver transplantation (LT) in pediatric Wilson disease (WD) with a specific sub-analysis in patients with neuropsychiatric symptoms. Methods: Demographic, operative, laboratory and neurologic findings of 23 pediatric patients with WD that underwent LT were analyzed by examining the patient charts. Results: Median age of the patients was 13 ( 7 to 17) years. Median Wilson’s Index scores of the patients were 7 (5-13). Median Child-Pugh Score, MELD-Na and PELD scores of the patients were 10 (5-12), 19 (8-34) and 25.4 (8.4-30.7); respectively. Eight patients (34.8%) had Kayser-Fleischer rings on examination Five patients (21.7%%) presented with acute decompensated Wilson’s disease. Fifteen patients (65.2%) received living donor liver transplantation. Totally, 10 patients (43,4%) had nervous system involvement in the preoperative period. Two patients fully recovered; 2 patients showed partial recovery. On the other hand, 4 patients showed no improvement and 2 patients had progression of their disease in the postoperative period. Conclusions: The results of the present study show that LT is an effective and safe alternative in end-stage liver failure in WD. However, in these patients, nervous system involvement may not improve despite successful LT.

High-Value-Care Case Based Management in Pediatric Wilson Disease

High-value care (HVC) is a term used for providing the best care possible for patients while simultaneously decreasing unnecessary expenses. HVC is a good instance of striking a balance between cost and benefit. Principles of value-based health care provide physicians with the necessary knowledge, tools, and strategies to improve the process of clinical reasoning. In this article, we present a case of Wilson’s disease in an 8-year-old boy as a clinical example of the impact of HVC on clinical decision-making and clinical reasoning

Brain MRI in the Decision for Liver Transplantation in Pediatric Neurological Wilson's Disease.

Neurological Wilson's disease (WD) presentation in the pediatric population is rare, and liver transplantation (LT) in these patients remains controversial. The aim of the present study was to assess the role of brain magnetic resonance imaging (MRI) in predicting reversion of brain lesions and neurological outcomes in pediatric WD patients after LT. Patients with confirmed WD (Leipzig score ≥4), disease onset in pediatric age (<18 years), neurological involvement, and submitted to LT were selected. Clinical records and pre- and post-LT brain MRI were evaluated. Six patients met the pre-defined inclusion criteria, one of whom died shortly after LT and was excluded. The indication for LT was end-stage liver disease in two patients and neurological worsening despite optimized treatment in three patients. After LT, the neurological picture progressively improved in all patients. Pre-LT brain MRI showed T1-weighted hyperintensities in four patients, which quickly resolved afterward. T2-weighted hyperintensities were observed in four patients before LT, completely resolving in one patient, stabilizing in two, and improving in one after LT. A direct correlation could not be found between clinical and neuroradiological improvement. Progressive clinical improvement was observed even in patients with irreversible brain MRI changes. Conversely, some patients with normal MRI had only slight neurological improvement. The pattern of T2-weighted hyperintensities after LT was unpredictable and did not correlate with neurological outcomes, suggesting that these changes may not entail irreversible clinical damage. Therefore, brain MRI does not seem to have prognostic value for assessing clinical response to LT.

Wilson Disease in Children; Chelation Therapy or Liver Transplantation? A 10-Year Experience from Pakistan.

BackgroundWilson disease (WD) is a rare genetic disorder with vast clinical presentations and a higher incidence in areas where consanguinity is common. Most patients can be treated with oral chelation, but some require advanced surgical intervention, like liver transplantation (LT). This study aims to review outcomes of WD patients presenting to a tertiary care center over a period of 10 years.Material/MethodsThis retrospective analysis was conducted at Shifa International Hospital, Islamabad, Pakistan. Patients <18 years who were diagnosed with WD per ESPAGHAN guidelines from 2010 to 2020 were included. Presentation, diagnosis, treatment, and LT and its complications were recorded. Follow-ups were recorded, and patients were contacted by phone in cases of interrupted follow-up. Frequencies and percentages of variables were calculated.ResultsA total of 48 patients with WD were identified. Symptomatic disease was seen in 45 patients, with 3 diagnosed on screening. The hepatic form was common (62.2%). Mean age at diagnosis was 9.74 (range 5–17) years, 28 (58.3%) were male, while 17 (35.4%) were female. Urinary copper was increased in all patients (645.82±528.40). Oral treatment with penicillamine was given to 34 (75.5%) patients; 4 (8.9%) died while on oral treatment. Living donor LT was performed in 11 (22.9%) patients, who had a mean King’s Wilson index of 11 (range, 6–14). Currently, all LT patients are alive, with maximum graft survival of 7 years.ConclusionsLT offers a promising treatment with good outcomes in pediatric WD. However, timely diagnosis and management with oral chelation therapy can prolong survival without LT.

ATP7B variant spectrum in a French pediatric Wilson disease cohort

Background/aimThe spectrum of ATP7B variants varies significantly according to geographic distribution, and there is insufficient data on the variants observed in the French population. MethodsClinical data of 113 children included in the French WD national registry were gathered from March 01, 1995 to July 01, 2020. Data included epidemiological, clinical, laboratory, genetics. ResultsDiagnosis was made at a mean age of 11.0 ± 4.1 years (range 1–18 years). At diagnosis, 91 patients (79.8 %) had hepatic manifestations, 18 (15.8 %) presented neurological manifestations, and 4 patients (3.5 %) were asymptomatic. Only 29 patients (25 %) were homozygous for a variant. We have found a total of 102 different variants including 14 novel variants. Recurrent variant p.His1069Gln was the most prevalent, n = 31 alleles (14,2%), with only seven homozygous; in contrast 55% of variants are identified in only one family. 45% were truncating variants. In respect of mutated exon, the three most prevalent were exon 14 (16.5%), exon 8 (13.8%), and exon 3 (11.5%). When considering patients with two Nonsense / Frameshift variants as a group and those with two Missense variants, we found significantly lower ceruloplasmin for the former: 2.8 ± 0.7 mg/dl vs 8.4 ± 5mg/dl (p<0.05). Conclusionp.His1069Gln is the most frequent variant (14,2%) and exons 14, 8, and 2 of the ATP7B gene account for 41.7% of total variants. However, there is significant heterogeneity in the French population concerning the other ATP7B variants. Nonsense / Frameshift variants were associated with lower ceruloplasmin levels.

Pediatric Wilson's Disease: Phenotypic, Genetic Characterization and Outcome of 182 Children in France.

To describe a cohort of Wilson disease (WD) pediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome. Clinical data of 182 pediatric patients included in the French WD national registry from 01/03/1995 to 01/06/2019 were gathered. Diagnosis of WD was made at a mean age of 10.7 ± 4.2 years (range 1-18 years). At diagnosis, 154 patients (84.6%) had hepatic manifestations, 19 (10.4%) had neurological manifestations, and 9 patients (4.9%) were asymptomatic. The p.His1069Gln mutation was the most frequently encountered (14% of patients).Neurological patients were diagnosed at least 1 year after they presented their first symptoms. At diagnosis, the median urinary copper excretion (UCE) was 4.2 μmol/24 hours (0.2-253). The first-line treatment was d-penicillamine (DP) for 131 (72%) patients, zinc salts for 24 (13%) patients, and Trientine for 17 (9%) patients. Liver transplantation was performed in 39 (21.4%) patients, for hepatic indications in 33 of 39 patients or for neurological deterioration in 6 of 39 patients, mean Unified Wilson's Disease Rating Scale of the latter went from 90 ± 23.1 before liver transplantation (LT) to 26.8 ± 14.1 (P < 0.01) after a mean follow-up of 4.3 ± 2.5 years. Overall survival rate at 20 years of follow-up was 98%, patient and transplant-free combined survival was 84% at 20 years. Diagnosis of WD can be challenging in children, particularly at the early stages of liver disease and in case of neurological presentation; hence the support of clinical scores and genetic testing is essential. Diagnosis at early stages and proper treatment ensure excellent outcomes, subject to good long-term treatment compliance. LT is a valid option for end-stage liver disease not responding to treatment and can be discussed for selected cases of neurological deterioration.

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices.

BACKGROUNDAcute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIMTo determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODSWe reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King’s College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.RESULTSAmong the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSIONWDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.

Acute pancreatitis complicating a case of pediatric Wilson's disease*

Acute pancreatitis complicating a case of pediatric Wilson's disease*

Pediatric Wilson Disease Presenting as Acute Liver Failure: An Individual Patient Data Meta-analysis.

Wilson disease (WD) presenting as acute liver failure (ALF) is rare and typically fatal without liver transplantation (LT). Its rarity has hindered comprehensive studies. We undertook an individual patient data meta-analysis to characterize a cohort of pediatric patients presenting with ALF whose final diagnosis was WD to examine outcomes and identify predictors of poor outcomes. Database searches were conducted in PubMed, ScienceDirect, and Google Scholar, restricted to English-language articles published between January 1984 and May 2018. Articles were excluded if pediatric (<18 years old) data were not extractable or if LT was not readily available at reporting institutions. Extracted data included clinical and biochemical characteristics, genotype, treatment, and outcome. Data were available on 249 subjects from 52 articles, plus 7 additional subjects identified from our institution's WD database (N = 256). Females represented 69% (n = 170/245). Median age at presentation was 13.4 years (n = 204, range 4.0-17.9). Of the total 256 subjects, 87% underwent LT, 11% achieved spontaneous recovery and 2% died before LT. International normalized ratio >2.0 at presentation was a predictor of LT/death (odds ratio 7.6, 95% confidence interval 1.5-28), with a trend observed for hepatic encephalopathy (HE) (odds ratio 4.18, 95% confidence interval 0.99-18). Arithmetic diagnostic scores proved inferior in the pediatric age-bracket compared to adults. This large international pediatric cohort has permitted an individual patient data analysis of WD presenting as ALF. Notably, 11% of subjects achieved spontaneous survival; the rest required LT. Coagulopathy (international normalized ratio >2:0) and HE at presentation heralded poor outcomes. Further prospective studies may identify additional early predictors of outcomes.

Retrospective analysis of long-term outcome 10 years after liver transplantation for Wilson disease: experience over three decades.

We evaluated long-term outcomes for patients with Wilson disease (WD) after liver transplantation (LT) and searched for risk factors for poor survival. Retrospective analysis of UNOS/OPTN data identified 156 pediatric and 515 adult cases of LT for WD between 1987 and 2016. Comparison cases were 10442 pediatric and 104874 adult non-WD transplant recipients. Survival was calculated using Kaplan-Meier analysis. Recipient, donor, and surgical variables were compared by Cox regression. Survival rates 3, 5, and 10years after LT for adult WD patients (87.5%, 85.4%, and 80.5%, respectively) were significantly higher than those for non-WD patients (P<0.001); survival rates for pediatric WD patients (90.5%, 89.7%, and 86.5%, respectively) did not differ significantly from non-WD patients. Graft survival in adult and pediatric patients followed similar trends. Regression analysis identified older age, female gender, and use of life support at the time of transplant as risk factors for decreased survival for adults with WD, and younger age, male gender, obesity, and high serum creatinine at the time of transplant as risk factors for poor survival in pediatric recipients with WD. Presentation with fulminant liver failure was not associated with survival in WD patients. No donor characteristic predicted poor survival. Long-term patient and graft survival after LT is excellent for both adult and pediatric WD patients.

Brain magnetic resonance spectroscopy (MRS) as a diagnostic tool for detecting early neurological changes in children with Wilson’s disease

PurposeAlthough brain magnetic resonance spectroscopy (MRS) imaging findings in adult Wilson disease (WD) have been explained in extensive details, a paucity of information currently exists regarding brain MRS imaging findings in pediatric WD. The purpose of this study was to clarify the role of brain MRS in detecting early metabolite abnormalities in children with WD. Patient and methodsA case-controlled prospective study included 26 children with WD and 26 healthy controls. All children were subjected to examination on a 1.5 T MRI scanner. The spectra of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), as well as the metabolite ratios of NAA/Cho, NAA/Cr, and Cho/Cr, were measured and compared between two groups. ResultsEight patients revealed increased signal intensity in the basal ganglia at T1-weighted images. When compared with healthy controls, WD patients showed a significant decrease (p < 0.05) in NAA (63.8 ± 9.6 vs 97.6 ± 3.8), Cho (46.7 ± 8.9 vs 87.3 ± 4.7), Cr (44 ± 10.1 vs 81.9 ± 4.05), NAA/Cho (1.92 ± 1.2 vs 3.34 ± 0.55), NAA/Cr (1.29 ± 0.7 vs 2.46 ± 0.34), and Cho/Cr (0.78 ± 0.4 vs 2 ± 0.13). Patients complicated with liver cell failure showed a significant decrease in all previous parameters (p < 0.05) than patients without complications. Patients with mixed neurological and hepatic diseases showed a severe reduction in NAA, NAA/Cr, and NAA/Cho compared with patients with hepatic disease only. ConclusionMRS in pediatric WD detects early neurological changes even with normal MRI.

56. A follow up study of symptomatic pediatric Wilson disease from a non-transplant tertiary center

56. A follow up study of symptomatic pediatric Wilson disease from a non-transplant tertiary center

7. AARC-ACLF score: best predictor of outcome in children and adolescents with decompensated Wilson's disease

Background and Aims: At present, there is an urgent need to identify ideal prognostic markers, in order to consider LT early in the course for decompensated Wilson's disease (WD) subjects, for best results. Recently, doubts have been raised about the universal application and efficacy of New Wilson's index (NWI) in predicting Liver Transplant (LT) or mortality in such cases. APASL (Asian Pacific Association for the Study of the Liver) ACLF (Acute on Chronic Liver Failure) Research Consortium (AARC) has introduced a new score (AARC-ACLF score) which has not been studied in these children. This work was thus planned to study the predictive risk factors or scores for mortality at 90 days in decompensated WD in children and adolescents. Methods: Data of all pediatric WD cases was prospectively collected and analyzed. Cox regression and Area under Receiver Operative Curve (AUROC) analysis were used to identify best predictive score for mortality at 90 days. Results: Sixty confirmed cases of decompensated WD, 35 (58.3%) improved on medical management and 25 (41.7%) either died (20) or were transplanted (5). Among those with NWI ≥ 11 (34/60 cases) 17 survived versus those with NWI < 11 (21/61), 3 died. NWI (HR 1.299, 95%CI 1.118–1.508, p = 0.001), AARC ACLF (HR 1.45, 95%CI 1.21–1.75, p = 0.001) and Chronic liver failure Sequential Organ failure Assessment score also known as CLIF SOFA (HR 1.26, 95%CI 1.11–1.49, p = 0.004) were all significantly associated with death on univariate Cox regression analysis. On comparative evaluation of the predictive scores in the present cohort, the highest positive (5.25) and lowest negative (0.12) likelihood ratios as well as highest accuracy (85.25%) revealed AARC ACLF as the best predictor of mortality. AARC ACLF had the best predictability with AUROC of 0.90 and the minimum standard error of 0.042 (Fig. 1). For every unit increase in AARC ACLF score, there is likelihood of 45% increase in 90 day mortality. The optimal cut off for the AARC ACLF was ≥11 with significantly better survival. Conclusions: AARC ACLF is the best score for the prediction of mortality at 90 days in decompensated WD cases. NWI has lower sensitivity and accuracy as a predictive tool for death in this cohort. While all patients’ with decompensated WD should be listed for LT, but an immediate LT is indicated if AARC ACLF ≥11 is present in the patient. The authors have none to declare.

Spectrum of Pediatric Wilson Disease From a Non-transplant Tertiary Care Center in North India

Spectrum of Pediatric Wilson Disease From a Non-transplant Tertiary Care Center in North India

Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.

Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b⁻/⁻ mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b⁻/⁻ mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.

Diagnostic Value of Ceruloplasmin in the Diagnosis of Pediatric Wilson's Disease.

PurposeMeasurement of serum ceruloplasmin level is the first step in screening for Wilson's disease (WD). Despite the rarity of WD in the general population, ceruloplasmin levels are routinely measured through hepatitis screening in both adults and children. Herein, we evaluated the diagnostic value of ceruloplasmin for the diagnosis of WD among children with hepatitis.MethodsWe retrospectively reviewed data on serum ceruloplasmin levels measured as a serologic marker for patients with hepatitis at Asan Medical Center (Seoul, Korea) between from January 2004 to November 2013. The diagnosis of WD was confirmed by the identification of pathogenic variants in the ATP7B gene. To determine the diagnostic accuracy of ceruloplasmin, receiver operation characteristic (ROC) curves were constructed and the area under curve (AUC) were calculated.ResultsMeasurements of serum ceruloplasmin were performed in 2,834 children who had hepatitis. Among these, 181 (6.4%) children were diagnosed with WD. The sensitivity, specificity, and accuracy of a ceruloplasmin level of <20 mg/dL in the discrimination of WD were 93.4%, 84.2%, and 84.8%, respectively. In this study, 418 (14.7%) false-positive cases and 12 (0.4%) false-negative cases were noted. Using a ROC curve, a ceruloplasmin level of ≤16.6 mg/dL showed the highest AUC value (0.956) with a sensitivity of 91.2%, a specificity of 94.9%, and an accuracy of 94.7%.ConclusionThe measurement of serum ceruloplasmin was frequently used for the screening of WD in children, despite a low positive rate. The diagnostic value of ceruloplasmin may be strengthened by adopting a new lower cut-off level.