New Way to Diagnosis of Wilson’s Disease: ATP7B Peptides

CJ Collins, F Yi et al. Gastroenterol 2021; 160: 2367-2382. Full text: Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease

There continues to be challenges in the diagnosis of Wilson’s disease (WD). Genetic testing, per the authors and Vasrome (, have found more than 649 pathogenic mutations and another 692 mutations that are VUS. Definitive diagnosis with genetic testing requires 2 known pathogenic variants. Other features, including Kayser-Fleischer rings and ceruloplasmin, have limited sensitivity and/or specificity.

Methods: Two hundred and sixty-four samples from biorepositories at 3 international and 2 domestic academic centers and 150 normal controls were used.

Key findings:

  • Two ATP7B peptides were found to have a sensitivity of 91.2%, specificity of 98.1%, positive predictive value of 98.0%, and a negative predictive value of 91.5%.
  • In patients with normal ceruloplasmin concentrations (>20 mg/dL), 14 of 16 (87.5%) were ATP7B-deficient. In patients without clear genetic results, 94% were ATP7B-deficient.

Discussion: As with other tests, ATPB7 peptide testing has limitations. Most patients with WD have pathogenic mutations that often result in protein misfolding, absence of decay of messenger RNA and enhanced degradation; hence, low ATPB7 levels; however, disease-causing mutations that affect protein activity but not protein concentration will generate false-negative results.

My take: “ATP7B peptide analysis identified WD patients in a large majority of cases and reduced ambiguities resulting from genetic analysis and Cp (ceruloplasmin) levels. This noninvasive assay can serve as an adjunctive test for the diagnosis of WD and is expected to fundamentally advance the use of proteomic technology for a rapid screening tool.

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