Wilson disease score

The Leipzig score combines the clinical features and tests for Wilson disease into a single diagnostic score. It is the scoring system used in the EASL guidelines.

Kayser-Fleischer rings

On slit lamp examination.

Present (+2)Absent (0)

Neuropsychiatric symptoms suggestive of Wilson disease, or typical brain MRISevere (+2)Mild (+1)Absent (0)

Coombs-negative haemolytic anaemia

With a high serum copper.

Present (+1)Absent (0)

24-hour urinary copper, in the absence of acute hepatitis

Upper limit of normal is usually 40 µg (0.6 µmol) a day.

Normal (0)1 to 2 times the upper limit of normal (+1)More than 2 times the upper limit of normal (+2)Normal, but more than 5 times the upper limit after a D-penicillamine challenge (+2)

Serum caeruloplasmin

By the nephelometric method.

Normal, above 0.2 g/L (0)0.1 to 0.2 g/L (+1)Below 0.1 g/L (+2)

Liver copper, in the absence of cholestasisNot measured (0)Normal: below 50 µg/g (0.8 µmol/g) dry weight (−1)50 to 250 µg/g (0.8 to 4 µmol/g) dry weight (+1)Above 250 µg/g (4 µmol/g) dry weight (+2)Not quantified, but rhodanine-positive granules on biopsy (+1)

ATP7B mutation analysisNot done, or no disease-causing mutation found (0)Disease-causing mutation on one chromosome (+1)Disease-causing mutations on both chromosomes (+4)

Answer all seven items.

Leipzig score	Interpretation
4 or more	Diagnosis established
3	Diagnosis possible; more tests needed
2 or less	Diagnosis very unlikely

Notes

A score of 3 usually calls for the next test in sequence: liver copper if not yet measured, or mutation analysis.
Caeruloplasmin is low in about 20% of heterozygous carriers, and in protein loss, malabsorption and severe liver failure of any cause. It rises with inflammation, oestrogen and pregnancy.
Urinary copper can be raised in cholestasis and in acute liver failure of any cause.
In acute liver failure, an ALP to bilirubin ratio below 4 and an AST to ALT ratio above 2.2 together suggest Wilson disease.
Screen first-degree relatives, particularly siblings.

References

Ferenci P, Caca K, Loudianos G, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23(3):139-142.

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol. 2012;56(3):671-685.