Can we suspect Wilson disease in this patient?

Wilson Disease Should Be Strongly Suspected in This Patient

Yes, Wilson disease must be actively considered and excluded in this clinical scenario, as it is a treatable condition with fatal consequences if missed, and the diagnostic approach should be systematic and comprehensive. 1, 2

When to Suspect Wilson Disease

Wilson disease should be suspected in any individual between ages 3 and 55 years with liver abnormalities of uncertain cause, and age alone should never exclude the diagnosis—patients have been diagnosed into their eighth decade. 1, 2, 3

Key Clinical Presentations Requiring High Suspicion

Hepatic manifestations that should trigger evaluation include:

• Asymptomatic elevation of aminotransferases (AST, ALT) found incidentally 2
• Asymptomatic hepatomegaly or isolated splenomegaly 2, 4
• Clinical picture resembling acute viral hepatitis 2
• Presentation mimicking autoimmune hepatitis, particularly in children or adults failing to respond rapidly to corticosteroid therapy 1
• Fatty liver or NASH-like findings on histology 1
• Compensated or decompensated cirrhosis of unclear etiology 2
• Fulminant hepatic failure with specific features (detailed below) 1

Neuropsychiatric manifestations warranting investigation:

• Tremor with characteristic "wing beating" appearance 1, 2
• Dysarthria (slurred speech) and drooling as early symptoms 1, 2
• Dystonia (focal, segmental, or severe) 1, 2
• "Juvenile Parkinsonism" (tremor-rigidity syndrome) 1, 2
• Deteriorating handwriting or micrographia 1, 2
• Declining school performance in children 1, 2
• Behavioral changes, personality changes, impulsiveness, labile mood 1, 2
• Depression, anxiety, or frank psychosis 1, 2

Other presentations that should raise suspicion:

• Coombs-negative hemolytic anemia, either isolated or with liver disease 1, 5, 2
• Renal abnormalities including aminoaciduria and nephrolithiasis 1, 2
• Premature osteoporosis or arthritis 1, 2
• Cardiomyopathy 1, 2
• Menstrual irregularities, infertility, or repeated miscarriages 1, 2

Fulminant Hepatic Failure: A Critical Presentation

Wilson disease presenting as fulminant hepatic failure has a characteristic pattern that distinguishes it from other causes and carries 95% mortality without liver transplantation. 1, 5

The diagnostic features include:

1. Coombs-negative hemolytic anemia with acute intravascular hemolysis 1
2. Coagulopathy unresponsive to parenteral vitamin K 1
3. Rapid progression to renal failure 1
4. Modest aminotransferase elevations (typically <2,000 IU/L), which is paradoxically lower than other causes of acute liver failure 1
5. Normal or markedly subnormal alkaline phosphatase (typically <40 IU/L) 1
6. Alkaline phosphatase to bilirubin ratio <2 1
7. Female predominance (2:1 to 4:1 female:male ratio) 1, 5

This presentation may mimic HELLP syndrome during pregnancy. 5, 2

Common Diagnostic Pitfalls to Avoid

Critical errors that delay diagnosis:

• Failing to consider Wilson disease in patients over 40 years—diagnosis has been made in the eighth decade 2, 3
• Misdiagnosing neuropsychiatric symptoms as primary psychiatric disorders—diagnostic delays up to 12 years have been reported 1, 2
• Attributing behavioral changes in children to puberty rather than investigating for Wilson disease 1, 2
• Assuming absence of Kayser-Fleischer rings excludes the diagnosis—they are absent in 50% of patients with hepatic presentations and even 10% with neurological disease 1, 2, 3
• Relying on ceruloplasmin alone—18% of patients with non-fulminant disease have neither Kayser-Fleischer rings nor low ceruloplasmin 3
• Accepting a diagnosis of autoimmune hepatitis without excluding Wilson disease, especially if response to corticosteroids is poor 1

Initial Diagnostic Approach

The diagnostic workup must be comprehensive and cannot rely on a single test:

1. Slit-lamp examination by an experienced ophthalmologist for Kayser-Fleischer rings (golden-brownish pigment near the limbus); if not visible on standard examination, gonioscopy should be performed 1, 2, 6

2. Serum ceruloplasmin (low in most but not all patients) 1, 3

3. 24-hour urinary copper excretion (elevated >100 μg/24h in symptomatic patients; can be massively elevated >800 μg/24h in fulminant cases) 1

4. Serum copper and non-ceruloplasmin copper calculation (total copper minus ceruloplasmin-bound copper; elevated in Wilson disease) 1

5. Liver function tests including aminotransferases, bilirubin, alkaline phosphatase, albumin, and INR 1

6. Complete blood count to assess for hemolysis 1

7. Liver biopsy with quantitative hepatic copper measurement (>250 μg/g dry weight is diagnostic, though patients on prior treatment may have lower levels) 1, 3

8. Genetic testing for ATP7B mutations can support diagnosis but should not be used alone—asymptomatic siblings with two mutations may have normal copper metabolism and not require treatment 2, 7

Why This Matters: Prognosis and Treatment

Untreated Wilson disease is universally fatal, with most patients dying from liver disease and a minority from neurological complications. 1 However, with appropriate treatment, prolonged survival has become the norm, making early diagnosis critical. 1

Treatment options include chelating agents (D-penicillamine, trientine) and zinc salts, which fundamentally change the natural history of the disease. 1, 8, 9 For fulminant hepatic failure or end-stage liver disease, urgent liver transplantation is life-saving. 1, 5

Family Screening Imperative

First-degree relatives of any newly diagnosed patient must be screened for Wilson disease, as presymptomatic treatment prevents disease manifestations entirely. 1 The evaluation should include history, physical examination, serum aminotransferases, ceruloplasmin, slit-lamp examination, and 24-hour urinary copper. 1