Wilson Disease is the Most Likely Diagnosis
The most likely laboratory abnormality in this 32-year-old man with tremor, neuropsychiatric symptoms, and elevated transaminases is a low serum ceruloplasmin level (<20 mg/dL), indicating Wilson disease. 1
Clinical Presentation Strongly Suggests Wilson Disease
This patient's constellation of findings is classic for Wilson disease:
Age and neuropsychiatric presentation: The patient is 32 years old, within the typical age range for Wilson disease presentation (ages 3-55), with neurologic manifestations most commonly appearing in the third decade 1
Tremor characteristics: The "arrested tremor" (likely asterixis or parkinsonian-like tremor) is a hallmark extrapyramidal finding in Wilson disease 1
Psychiatric history: The 5-year history of depression and emotional lability requiring two hospitalizations aligns with Wilson disease's psychiatric manifestations, which include depression, personality changes, and psychosis 1
Cognitive dysfunction: Inability to focus on tasks and headaches are consistent with the cognitive impairment seen in Wilson disease 1
Hepatitis history: Two prior hospitalizations for "unknown type of hepatitis" suggest undiagnosed chronic liver disease, as Wilson disease commonly presents with unexplained liver abnormalities 1
Liver Enzyme Pattern Supports Wilson Disease
The transaminase levels (AST 280, ALT 290) are characteristic:
Moderate elevation: In Wilson disease, serum aminotransferase activities are generally abnormal but the degree of elevation is often mild and does not reflect the severity of liver disease 1
AST/ALT ratio: The ratio here is approximately 0.97, which is consistent with Wilson disease. While alcoholic liver disease typically shows AST/ALT >2, Wilson disease usually presents with ratios closer to 1.0 2, 3
Levels rarely exceed 300 IU/L: The transaminase levels of 280-290 IU/L fit the typical pattern, as AST levels are rarely above 300 U/mL in Wilson disease 2
Expected Laboratory Abnormalities on Additional Testing
Primary diagnostic findings 1:
- Low ceruloplasmin (<20 mg/dL): Present in the vast majority of Wilson disease patients, though not entirely specific
- Elevated 24-hour urinary copper (>40 μg/day or >0.6 μmol/day): Confirms excessive copper excretion
- Kayser-Fleischer rings on slit-lamp examination: Should be sought, though their absence does not exclude Wilson disease, particularly in patients presenting primarily with liver disease 1
Additional supportive findings 1:
- Elevated total bilirubin (3.2 mg/dL already noted) may indicate hemolysis or advanced liver disease
- Low serum copper (paradoxically low despite copper overload)
- Molecular testing showing ATP7B gene mutations confirms diagnosis
Critical Diagnostic Algorithm
Wilson disease must be excluded in any patient with unexplained liver disease along with neurological or neuropsychiatric disorder 1
The diagnostic approach should proceed as follows 1:
- Measure serum ceruloplasmin immediately: If <20 mg/dL, Wilson disease is highly likely
- Order 24-hour urinary copper collection: Ensure adequacy of collection; >40 μg/day supports diagnosis
- Arrange slit-lamp examination: By skilled examiner to identify Kayser-Fleischer rings
- Consider molecular testing: If ceruloplasmin and urinary copper are equivocal, ATP7B mutation analysis confirms diagnosis
Why Not Hepatic Encephalopathy?
While this patient has liver dysfunction and neuropsychiatric symptoms, hepatic encephalopathy is less likely:
- Asterixis pattern: True asterixis in hepatic encephalopathy is a "flapping tremor" or negative myoclonus, not an "arrested tremor" 1
- Chronic progressive course: The 5-year history of depression and two prior hepatitis episodes suggest chronic progressive disease rather than episodic hepatic encephalopathy 1
- Lack of disorientation: Hepatic encephalopathy typically presents with disorientation as a key marker of overt disease 1
- Young age with extrapyramidal signs: The prominent extrapyramidal dysfunction (tremor, rigidity) in a young patient points more toward Wilson disease than hepatic encephalopathy 1
Common Pitfalls to Avoid
Do not dismiss Wilson disease based on age alone: While most present between ages 5-35, cases have been diagnosed in patients up to their eighth decade 1
Do not assume normal ceruloplasmin excludes Wilson disease: Approximately 5-10% of Wilson disease patients may have normal or near-normal ceruloplasmin levels, particularly those with neurologic presentations 1
Do not overlook Wilson disease in patients with apparent autoimmune hepatitis: Patients with Wilson disease may have elevated serum immunoglobulins and detectable autoantibodies, mimicking autoimmune hepatitis 1
Do not delay treatment pending genetic confirmation: If clinical suspicion is high with supportive biochemical findings, treatment should be initiated promptly as Wilson disease is highly treatable but progressive if untreated 1