The utility of whole exome sequencing in diagnosing Wilson disease: A case report.

Abstract

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene, resulting in toxic copper accumulation in the body. Diagnosis is typically based on biochemistries, including low serum ceruloplasmin and elevated 24-h urine copper excretion, with Kayser-Fleischer (KF) rings being a supportive feature. We describe a 7-year-old girl who presented with isolated elevation of serum alanine aminotransferase (ALT), low serum ceruloplasmin, and presence of nonspecific autoantibodies. Liver biopsy revealed elevated hepatic copper content (241 μg/g dry weight), mild macrovesicular steatosis, negative copper staining and no KF rings. Targeted genetic testing identified a single pathogenic ATP7B variant, and whole exome sequencing (WES) later revealed a second variant of uncertain significance (VUS). Repeat liver biopsy showed hepatic copper content of 258 mcg/g, meeting diagnostic criteria. The patient was started on trientine, and ALT normalized within 3 months, with increased urinary copper excretion. This case underscores how WD can mimic autoimmune hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD), and how diagnosis may rely on integrating histologic findings, genetic data, and therapeutic response.