Wilson Disease Diagnosis
Clinical Presentation
- Wilson disease should be considered in individuals between 3 and 55 years with liver abnormalities of uncertain cause, and must be excluded in patients with unexplained liver disease along with neurological or neuropsychiatric disorders 1
- The American Association for the Study of Liver Diseases recommends considering Wilson disease in patients with liver manifestations, such as unexplained elevated liver enzymes, chronic hepatitis, or cirrhosis of unknown etiology, and neurological manifestations, such as movement disorders or deterioration in handwriting 1, 2
- Psychiatric manifestations, including behavioral changes, personality disorders, depression, anxiety, or psychosis, can also be indicative of Wilson disease 1
- Other presentations, such as hemolytic anemia, renal abnormalities, skeletal abnormalities, or cardiomyopathy, may also suggest Wilson disease 2
Diagnostic Criteria
- The European Association for the Study of the Liver suggests that a diagnosis of Wilson disease can be established with a score of ≥4 using the Leipzig scoring system, which includes parameters such as Kayser-Fleischer rings, neurological symptoms, serum ceruloplasmin, hemolytic anemia, liver copper, urinary copper, and ATP7B mutation 3
- The Leipzig scoring system assigns points as follows:
| Parameter | Points |
|---|---|
| Kayser-Fleischer rings | |
| Present | 2 |
| Absent | 0 |
| Neurological symptoms | |
| Severe | 2 |
| Mild | 1 |
| Absent | 0 |
| Serum ceruloplasmin | |
| Normal (>0.2 g/L) | 0 |
| 0.1-0.2 g/L | 1 |
| <0.1 g/L | 2 |
| Hemolytic anemia | |
| Present | 1 |
| Absent | 0 |
| Liver copper | |
| >5× ULN (>4 μmol/g) | 2 |
| 0.8-4 μmol/g | 1 |
| Normal (<0.8 μmol/g) | -1 |
| Urinary copper | |
| >2× ULN | 2 |
| 1-2× ULN | 1 |
| Normal | 0 |
| ATP7B mutation | |
| On both chromosomes | 4 |
| On one chromosome | 1 |
| No mutations detected | 0 |
- A score of 3 indicates a possible diagnosis, while a score of ≤2 makes the diagnosis unlikely 3
Laboratory Tests
- The American Association for Clinical Chemistry recommends measuring serum ceruloplasmin, 24-hour urinary copper excretion, and performing a slit-lamp examination for Kayser-Fleischer rings to aid in the diagnosis of Wilson disease 2, 3
- Liver function tests, including alkaline phosphatase and bilirubin, can also be useful in establishing a diagnosis 2
- A ratio of alkaline phosphatase to bilirubin <2 can be suggestive of Wilson disease in patients with acute liver failure 2
Special Considerations
- The American Academy of Pediatrics recommends considering Wilson disease in children with apparent autoimmune hepatitis, as they may not respond to corticosteroids 1, 2
- First-degree relatives of patients with Wilson disease should be screened, including history and physical examination, serum aminotransferases and liver function tests, ceruloplasmin level, 24-hour urinary copper, slit-lamp examination for Kayser-Fleischer rings, and genetic testing if mutations are known in the index case 2, 4
- False-negative ceruloplasmin levels can occur in 15-36% of patients with Wilson disease, especially in those with active inflammation, while false-positive levels can occur in malabsorption, aceruloplasminemia, heterozygous carriers, and severe hepatic insufficiency 4, 3
- The absence of Kayser-Fleischer rings does not exclude Wilson disease, especially in hepatic presentations where they may be absent in up to 50% of cases 1