What blood tests should be ordered to work up a tremor in a younger adult, particularly if there is a history of liver disease?

Blood Tests for Tremor Workup in a Younger Adult with Liver Disease

In a younger adult with tremor and liver disease history, immediately order serum ceruloplasmin, 24-hour urinary copper excretion, and comprehensive metabolic panel to rule out Wilson disease, which is a treatable cause of both tremor and liver disease that must not be missed. 1

Critical First-Line Testing

Wilson Disease Screening (Mandatory)

• Serum ceruloplasmin is the essential first test, with levels <50 mg/L (<5 mg/dL) providing strong evidence for Wilson disease, though 10-20% of Wilson disease patients have normal ceruloplasmin levels 1
• 24-hour urinary copper excretion should be measured simultaneously, as basal urinary copper >100 μg/24 hours supports Wilson disease diagnosis 1
• Hepatic copper content >4 μmol/g dry weight on liver biopsy provides the best biochemical evidence, though sensitivity improves when threshold is lowered to 1.2 μmol/g dry weight (96.5% sensitivity) 1
• Slit-lamp examination for Kayser-Fleischer rings must be performed by an ophthalmologist, as these corneal copper deposits are pathognomonic when present with low ceruloplasmin 1

Essential Metabolic and Hepatic Panel

• Comprehensive metabolic panel including AST, ALT, alkaline phosphatase, bilirubin, albumin, and electrolytes to assess liver synthetic function and identify metabolic derangements 1
• Complete blood count to evaluate for Coombs-negative hemolytic anemia (seen in fulminant Wilson disease) and thrombocytopenia (suggesting portal hypertension) 1
• Prothrombin time/INR to assess hepatic synthetic function 1

Secondary Testing Based on Initial Results

If Wilson Disease Screening is Negative

• Thyroid function tests (TSH, free T4) to exclude thyrotoxicosis, which causes enhanced physiologic tremor and can present with liver enzyme elevations 2, 3
• Hemoglobin A1c and fasting glucose to assess for diabetes-related metabolic tremor 2, 3
• Serum alcohol level and GGT if alcohol-related liver disease is suspected, as alcohol withdrawal causes action tremor 1

Additional Liver Disease Workup

• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) to screen for chronic hepatitis B 1
• Hepatitis C antibody in high-risk patients or those with unexplained liver disease 1
• Autoimmune markers (ANA, anti-smooth muscle antibody, anti-LKM) if autoimmune hepatitis is suspected, as Wilson disease can mimic autoimmune hepatitis 1
• Alpha-1 antitrypsin level and serum ferritin with transferrin saturation to exclude other hereditary liver diseases 1

Critical Diagnostic Pitfalls

Wilson Disease Cannot Be Excluded by Normal Ceruloplasmin Alone

• 10-20% of Wilson disease patients have ceruloplasmin >200 mg/L (>20 mg/dL), and up to 20% of heterozygotes have decreased ceruloplasmin without disease 1
• Normal ceruloplasmin does NOT exclude Wilson disease, particularly in patients with neurologic symptoms and liver disease 1
• If clinical suspicion remains high despite normal ceruloplasmin, proceed directly to hepatic copper quantification and genetic testing for ATP7B mutations 1

Age Should Not Exclude Wilson Disease Consideration

• While most Wilson disease presents between ages 5-35, cases have been diagnosed in patients up to their eighth decade 1
• The combination of tremor (particularly parkinsonian or dystonic tremor) with any liver disease in a patient under 40 requires Wilson disease exclusion 1, 2, 4

Specific Wilson Disease Presentations Requiring Urgent Recognition

• Fulminant hepatic failure with Coombs-negative hemolysis, modest AST/ALT elevations (<2000 IU/L), low alkaline phosphatase (<40 IU/L), and alkaline phosphatase-to-bilirubin ratio <2 is pathognomonic for Wilson disease 1
• Neurologic Wilson disease manifests as movement disorders including parkinsonian tremor, dystonia, or choreiform movements, often with dysarthria and drooling 1

Algorithmic Approach to Blood Testing

Step 1: Order ceruloplasmin, 24-hour urinary copper, CBC, comprehensive metabolic panel, and PT/INR immediately 1

Step 2: If ceruloplasmin <200 mg/L OR urinary copper >100 μg/24h OR unexplained liver disease with neurologic symptoms, arrange slit-lamp examination and refer to hepatologist for liver biopsy consideration 1

Step 3: If Wilson disease excluded and tremor persists, add thyroid function tests, hemoglobin A1c, and viral hepatitis serology 1, 2

Step 4: Consider autoimmune markers, alpha-1 antitrypsin, and iron studies if liver disease etiology remains unclear 1