Assessment of the diagnostic value of serum ceruloplasmin for Wilson's disease in children

Abstract

Background: Serum ceruloplasmin is one of the major diagnostic parameters for Wilson's disease (WD). Age and gender difference of serum ceruloplasmin remain controversy. This study aims to assess diagnostic value of serum ceruloplasmin level for WD in children up to age of 15 years.

Methods: Serum ceruloplasmin levels were measured in 317 WD patients, 21 heterozygotes, 372 healthy control children and 154 non-WD patients with other liver diseases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic accuracy of serum ceruloplasmin for WD in children.

Results: Among healthy controls, serum ceruloplasmin level was slightly low in the infants younger than 6 months, and then maintained from 26 to 33 mg/dl after age of 6 months. A total of 8.1% of healthy children had levels of serum ceruloplasmin < 20 mg/dL. Serum ceruloplasmin level was 5.7 ± 4.7 mg/dl in WD patients, and 25.6 ± 5.9 mg/dl in heterozygous carriers. Only 1.9% of WD patients had serum ceruloplasmin levels > 20 mg/dL. Serum ceruloplasmin levels had gender difference, being higher in healthy boys than healthy girls, and higher in asymptomatic WD boys than asymptomatic WD girls (p < 0.01, p < 0.05). Serum ceruloplasmin levels also presented genotypic difference. WD patients with R778L homozygotes exhibited lower levels of serum ceruloplasmin than the patients without R778L (p < 0.05). The ROC curve revealed that serum ceruloplasmin level, at a cutoff value of 16.8 mg/dL, had the highest AUC value (0.990) with a sensitivity of 95.9% and a specificity of 93.6%.

Conclusions: Serum ceruloplasmin is one of sensitive diagnostic biomarkers for WD in children. Gender and genotypic difference of serum ceruloplasmin level should be considered. The cutoff value of serum ceruloplasmin level < 16.8 mg/dL may provide the highest accuracy for diagnosis of WD in children.

Keywords: Ceruloplasmin; Children; Diagnosis; Wilson’s disease.

Fig. 1

Gender difference of serum ceruloplasmin was analyzed among healthy children, WD patients and heterozygotes. A There were no significant gender differences of serum ceruloplasmin levels intra each age subgroup among WD patients and among healthy children. B Serum ceruloplasmin level was higher in boys than girls among healthy children (p < 0.01) and also among WD patients (p < 0.05). The mean levels of serum ceruloplasmin in WD patients were much lower than that in healthy controls and heterozygotes

Fig. 2

Receiver operating characteristic (ROC) curves of serum ceruloplasmin for the diagnosis of Wilson’ disease (WD). A When analyzing WD patients together with heterozygotes and non-WD patients, the area under the curve (AUC) was 0.990 (95% confidence interval (CI), 0.985–0.995). B When analyzing WD patients with acute liver failure and non-WD patients with acute liver failure, the area under the curve was 0.952 (95% confidence interval (CI), 0.885–1). C When analyzing asymptomatic WD patients and non-WD patients with viral hepatitis, the area under the curve was 0.994 (95% confidence interval (CI), 0.988–1). D–F Box and whisker plots show the values of serum ceruloplasmin in all WD and non-WD patients (D), the patients with acute liver failure and the patients (E) with elevated aminotransferases (F). The black line represents the consensus cutoff of serum ceruloplasmin (20 mg/dL). The dash lines in D–F represent the cutoff values obtained in the ROC curves of A–C (16.9 mg/dL, 16.0 mg/dL and 16.9 mg/dL), respectively.