Note: This guideline has been updated. The National Guideline Clearinghouse (NGC) is working to update this summary. The recommendations that follow are based on the previous version of the guideline.
Recommendations are followed by quality of evidence ratings (Grade I-IV) which are defined at the end of the "Major Recommendations" field.
Clinical Features
Wilson disease (WD) should be considered in any individual between the ages of 3 and 45 years with liver abnormalities of uncertain cause (Grade III).
In a patient in whom WD is suspected Kayser-Fleischer rings should be sought by slit-lamp examination by a skilled examiner. The absence of Kayser-Fleischer rings does not exclude the diagnosis of WD, even in patients with predominantly neurologic disease (Grade III).
Diagnostic Testing
Ceruloplasmin
Serum ceruloplasmin should be routinely measured during the evaluation of unexplained hepatic, neurologic, or psychiatric abnormalities in children and adults through middle age. An extremely low serum ceruloplasmin level (<50 mg/L or <5 mg/dL) should be taken as strong evidence for the diagnosis of WD. Modestly subnormal levels suggest that further evaluation is necessary. Serum ceruloplasmin within the normal range does not exclude the diagnosis (Grade III).
Urinary Copper Excretion
The basal 24-hour urinary excretion should be measured as an aid to the diagnosis of WD. Basal 24-hour urinary excretion of copper in WD is typically greater than 100 micrograms (1.6 micromoles) in symptomatic patients, but a finding greater than 40 micrograms (>0.6 micromoles or >600 nmoles) may indicate WD and requires further investigation (Grade II).
In children, penicillamine challenge studies may provide evidence for the diagnosis of WD if urinary excretion of greater than 1,600 micrograms copper/24 hours (>25 micromoles/24 hours) is found following the administration of 500 mg of D-penicillamine at the beginning and again 12 hours later during the 24-hour urine collection. The predictive value of this test in adults is unknown (Grade II).
Hepatic Parenchymal Copper Concentration
Hepatic parenchymal copper content greater than 250 micrograms/g dry weight provides critical diagnostic information and should be obtained in cases where the diagnosis is not straightforward and in younger patients. In untreated patients, normal hepatic copper content (<40 to 50 micrograms/g dry weight) excludes a diagnosis of WD (Grade III).
Neurological Evaluation and Radiologic Imaging of the Brain
Neurologic evaluation and radiologic imaging of the brain, preferably by magnetic resonance imaging (MRI), should be considered prior to treatment in all patients with neurologic WD and should be part of the evaluation of any patient presenting with neurologic symptoms consistent with WD (Grade III).
Genetic Studies
When possible, genetic diagnosis based on haplotype analysis should be used for family screening of first-degree relatives of patients with WD (Grade III).
Diagnostic Considerations in Specific Target Populations
"Mimic" Liver Diseases
Patients in the pediatric age bracket who present a clinical picture of autoimmune hepatitis should be investigated for WD. Adult patients with atypical autoimmune hepatitis or who respond poorly to standard corticosteroid therapy should also be investigated for WD (Grade III).
WD should be considered in the differential diagnosis of patients presenting with nonalcoholic fatty liver or who have pathologic findings of nonalcoholic steatohepatitis (NASH) (Grade IV).
Fulminant Liver Failure
WD should be suspected in any patient presenting with fulminant hepatic failure with Coombs-negative intravascular hemolysis, modest elevations in serum aminotransferases, low serum alkaline phosphatase, and ratio of alkaline phosphatase to bilirubin of less than 2 (Grade III).
Family Screening
First-degree relatives of any patient newly diagnosed with WD must be screened for WD. Assessment should include history and physical examination, serum aminotransferases and biochemical tests of hepatic synthetic function, complete blood count, and ceruloplasmin. Kayser-Fleischer rings should be sought by slit-lamp examination. The basal 24-hour urinary copper excretion should be measured. Genotype or haplotype studies based on findings in the proband should be performed (Grade II).
Treatment
Initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientine) (Grade II).
Treatment of presymptomatic patients or maintenance therapy of successfully treated symptomatic patients can be accomplished with the chelating agent penicillamine or trientine, or with zinc (Grade II).
Treatment in Specific Clinical Situations
Fulminant Hepatic Failure
Patients with fulminant hepatic failure or patients with severe liver disease unresponsive to chelation treatment should be treated with liver transplantation (Grade II).
Pregnancy
Treatment for WD should be continued during pregnancy, but dosage reduction is advisable for D-penicillamine and trientine (Grade III).
Liver Transplantation
Treatment is lifelong and should not be discontinued, unless a liver transplantation has been performed (Grade II).
Monitoring
For routine monitoring, serum copper and ceruloplasmin, liver biochemistries and international normalized ratio, and physical examination should be performed regularly (Grade III).
Twenty-four–hour urinary excretion of copper while on medication should be measured yearly, or more frequently if there are issues of compliance or if dosage of medications is adjusted. The serum nonceruloplasmin-bound copper may be estimated in these situations (Grade III).
Patients receiving chelators require a complete blood count with differential and urinalysis regularly no matter how long they have been on treatment (Grade III).
Definitions:
Quality of Evidence
Grade I Evidence from multiple well-designed randomized controlled trials each involving a number of participants to be of sufficient statistical power
Grade II Evidence from at least one large well-designed clinical trial with or without randomization, from cohort or case-control analytic studies, or well-designed meta-analysis
Grade III Evidence based on clinical experience, descriptive studies, or reports of expert committees
Grade IV Not rated