An incidental heterozygous ATP7B nonsense variant leading to a diagnostic pitfall for Wilson disease: a pediatric case report

Abstract Background Wilson disease (WD) is an autosomal recessive disorder caused by pathogenic variants in ATP7B, resulting in impaired copper transport and progressive copper accumulation, most prominently affecting the liver. With the growing use of genetic testing, incidental detection of ATP7B pathogenic/likely pathogenic variants in individuals without typical hepatic phenotypes can prompt overdiagnosis and unnecessary investigations. This case highlights the importance of interpreting a single heterozygous ATP7B variant in the context of phenotype and a standardized biochemical diagnostic pathway for WD. Case presentation A 13-year-old boy presented with brief paroxysmal attacks for >1 year, markedly worsened over the preceding month. Episodes were triggered by rising from sitting, characterized by transient postural instability with unilateral head deviation and ipsilateral dystonic/choreiform movements, lasted ~10 seconds, and resolved spontaneously. Consciousness was preserved, with no incontinence, convulsions, or postictal symptoms. Interictal neurological examination was normal. Ambulatory EEG monitoring captured three typical attacks without epileptiform discharges or ictal EEG correlates, and brain MRI was unremarkable. A slit-lamp examination revealed no Kayser–Fleischer ring. A low serum copper level (9.43 μmol/L; reference 10.50–29.90) prompted further evaluation; genetic testing incidentally identified a heterozygous ATP7B variant (NM_000053.4:c.2851C>T; p.Gln951Ter), reported as likely pathogenic. WD was considered. However, ceruloplasmin was normal (231.6 mg/L; reference 200.0–420.0), copper oxidase was normal (0.372 OD; >0.200), liver biochemistry was normal (ALT 11 U/L, AST 16 U/L, GGT 14 U/L; bilirubin within reference range), and abdominal ultrasound showed a normal liver and biliary tree. Urinary copper was reported as not elevated (quantitative 24-h value not available). Overall, findings did not support WD. Conclusions This case illustrates a diagnostic pitfall: incidental heterozygous ATP7B nonsense variants may lead to anchoring bias toward WD in individuals without hepatic phenotypes. WD diagnosis should rely on integrated clinical and standardized copper-metabolism evidence, avoiding attribution based on genetics or a single biochemical abnormality alone.