* The serum copper concentration should also be determined. It is decreased in proportion to the reduction in serum ceruloplasmin and can be used to monitor therapy. ¶ If the serum ceruloplasmin is ≥20 mg/dL (200 mg/L) and Kayser-Fleischer rings are present, a liver biopsy or molecular genetic testing is required regardless of the 24-hour urine copper. Δ Ensure adequate urine collection. ◊ For patients with neurologic disease but no evidence of liver disease, molecular genetic testing should be done first; for patients with liver disease, either molecular genetic testing or liver biopsy may be done first. If molecular genetic testing is positive, the diagnosis is confirmed. If negative, liver biopsy should be performed. On liver biopsy, a diagnosis of Wilson disease is established if the hepatic copper concentration is ≥250 mcg/g dry weight; a diagnosis is excluded if the hepatic copper concentration is <50 mcg/g dry weight; if the hepatic copper concentration is ≥50 and <250 mcg/g dry weight, molecular genetic testing for mutations in ATP7B should be performed (if not already done) to establish or exclude the diagnosis. § Most patients with Wilson disease are compound heterozygotes. The identification of one mutation supports the diagnosis, and the identification of two mutations confirms the diagnosis. Refer to UpToDate topics on the diagnosis of Wilson disease for additional discussion of genetic testing.
