Non-invasive testing for Wilson disease: Revisiting the d-penicillamine challenge test

Abstract

Wilson disease must be considered in patients with unexplained liver disease, in patients with liver disease and neurological or psychiatric symptoms or for first degree relatives of patients. The diagnosis of Wilson disease is most challenging in the pediatric population where most patients present with liver disease and Kayser-Fleischer rings are frequently absent. The spectrum of liver disease ranges from asymptomatic to cirrhosis and acute liver failure. The group with acute liver failure is the most easily recognized as having Wilson disease by virtue of the presence of non-immune hemolytic anemia and a low serum alkaline phosphatase level (yielding a serum alkaline phosphatase to bilirubin ratio <2). The remaining patients are first examined for signs of chronic liver disease and by slit lamp exam for corneal Kayser-Fleischer rings, tested for liver synthetic dysfunction and evidence of hepatic inflammation and for levels of serum ceruloplasmin and urinary copper excretion. If there remains suspicion of disease, a liver biopsy is recommended, the histology examined and the content of copper in the specimen quantitated. Prior to the more widespread use of transjugular liver biopsies, coagulopathy often precluded the performance of biopsy by percutaneous means. This led to a reliance on urine copper excretion and promotion of stimulation testing with the copper chelator d-penicillamine as a non-invasive means for diagnosing Wilson disease. More recently our armamentarium for diagnostic testing for Wilson disease has expanded to include