Serum levels of ceruloplasmin may be an important biomarker for the diagnosis of Wilson Disease (WD), according to a large Chinese study published in Frontiers in Neurology.

An optimal ceruloplasmin level cutoff of 0.13 g/L was determined using a receiver operator characteristic (ROC) curve. This suggested cutoff is slightly lower than the conventional cutoff of <0.2 g/L.

Using the new cutoff yielded an area under the curve (AUC) of 0.99 with a sensitivity of 97.0%, specificity of 96.1%, and accuracy of 96.5%. These values were in contrast to the traditional cutoff, which yielded a sensitivity of 99.8% but a specificity of 69.5% and an accuracy of 81.9%. 

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The traditional cutoff resulted in a false-positive rate of 30.5%. The most non-WD etiologies related to the decreased ceruloplasmin levels were liver failure, non-WD hepatitis, nephrotic syndrome, and heterozygous relatives. A total of 27.10% of patients with liver failure had ceruloplasmin levels below 0.20 g/L.

Correlations were also found between ceruloplasmin levels and disease phenotypes. Patients with an asymptomatic phenotype had lower levels (0.024 g/L; interquartile range (IQR), 0.014-0.047) compared to those with the hepatic subtype (0.034 g/L; IQR, 0.016-0.063; P <.093). 

Patients with a younger age at symptom onset also tended to have lower ceruloplasmin levels. Those with an onset age <10 years (0.022 g/L) were significantly lower than those with an age greater than 30 years (0.059 g/L; P <.001).

Regarding genotypes, patients with homozygous mutations had lower ceruloplasmin levels than those who were heterozygous or had no identified variants. Of the homozygous patients, those with the R778L/R778L variant (0.017 g/L) had lower levels than those with P992L/P992L (0.034 g/L) and other homozygous genotypes (0.045 g/L).

No significant differences were observed in ceruloplasmin levels between sexes or the presence of a K-F ring.

“Our work determined the optimal cutoff value of serum ceruloplasmin levels for the diagnosis of WD and identified differences in serum ceruloplasmin levels with respect to the age of symptom onset and ATP7B mutations, which may provide some valuable insights into the diagnosis and counsel of patients with WD,” the authors said.

Data on 3548 participants (1278 patients with WD and 2270 controls) were evaluated to retrospectively derive the ceruloplasmin cutoff values. The new values were then validated on a separate cohort of 313 participants (203 WD patients and 110 controls).

Reference

Yang Y, Hao W, Wei T, et al. Role of serum ceruloplasmin in the diagnosis of Wilson’s disease: A large Chinese study. Front Neurol. 2022;13. doi:10.3389/fneur.2022.1058642