Cryptic Presentations of Neurologic Wilson Disease With ATP7B Peptide Assessments

To illustrate the phenotypic variability in neurologic Wilson disease (NWD) and diagnostic value of ATP7B peptide testing in resolving WD cases.

We conducted a case series analysis of 3 individuals with suspected NWD. Clinical presentation, diagnostic workup including traditional biomarkers, genetic testing, and ATP7B peptide quantification by immuno-selected reaction monitoring mass spectrometry were reviewed.

The 3 patients demonstrated diverse neurologic presentations: (1) an adult with coexisting Parkinson disease and WD, exhibiting parkinsonian features with partial response to dopaminergic therapy; (2) a child with early-onset dystonia and neuropsychiatric symptoms; and (3) an adult initially misdiagnosed with multiple sclerosis. In these cases, ATP7B peptide testing revealed either markedly reduced or undetectable levels, confirming WD.

These cases emphasize the diagnostic complexity of NWD. ATP7B peptide analysis via immuno-SRM-MS provided direct evidence of ATP7B protein deficiency and confirmed variant pathogenicity demonstrating its use as a rapid, noninvasive, functionally informative diagnostic adjunct. As the assay is further validated and piloted for newborn screening, it holds promise for improving early detection and clinical outcomes in WD.