Table 1. Summary of studies applying the Leipzig score criteria.
| Ref. No. | Population and study design | Main findings | Laboratory cutoffs |
|---|---|---|---|
| Koppikar, 2005, United Kingdom (47) | Retrospective cohort study of 142 children with liver disease investigated for WD in the differential diagnosis, or screened after an index case of WD in the family | • 53 of 54 WD had a score ≥4 | • Liver copper >250 mg % dry weight |
| • 3 patients in the non-WD group had a score ≥4 | • Serum ceruloplasmin <20 g/L | ||
| • Sensitivity 98.14% | • Urine copper (pre-penicillamine) >1 mmol/24 h, post-penicillamine 425 mmol/24 h | ||
| • Specificity 96.59% | |||
| • PPV 94.64% | |||
| • NPV 98.83% | |||
| Moores, 2012, Canada (48) | Retrospective cohort study of 48 adult WD patients in the ambulatory setting | • 44 of 59 patients had a LS ≥4 | • Ceruloplasmin <0.20 g/L |
| • Median LS in neurological presenting patients was 8, which was significantly higher (P=0.002) compared with those with hepatic presentation (median 5) and asymptomatic presentation (median 6) | • Urinary copper >0.60 μmol/L | ||
| • Serum copper <11.3 μmol/L | |||
| • 81% of patients had serum copper values below the LLN | • Hepatic copper >0.80 μmol/g | ||
| Penon-Portmann, 2019, Costa Rica (49) | Retrospective cohort study of 140 pediatric WD patients with molecular ATP7B testing between 2010 and 2015 | • 100% sensitivity: A total of 34 pediatric patients, from 28 families, were confirmed to have WD by a score ≥4 points according to the LS | Ceruloplasmin lower normal limit (defined as 0.1 g/L or 28 IU/L) |
| • From the 34 diagnosed patients, 23 were new and 11 had been previously reported | |||
| Xuan, 2007, Canada (22) | Prospective study of adult patients with atypical presentations of Wilson Disease (n=3) | • All three of cases showed that the LS provides a useful framework for diagnosis | • 24-hour urine copper >0.6 lmol/24 h |
| • Even without the additional points from positive mutational analysis, all three patients each scored a 6, placing them in the diagnostic range | • Serum ceruloplasmin <0.20 g/L | ||
| • Hepatic copper content <50 lg/g | |||
| Abdel Ghaffar, 2011, Egypt (50) | Retrospective cohort study of 77 pediatric Wilson Disease patients from 50 unrelated families | • 73 patients with LS ≥4; only 4 children with LS of less than 4 (two asymptomatic and two hepatic); none of whom did mutational analysis at the time of scoring | • Serum ceruloplasmin <20 mg/dL |
| • The study concludes that the value given to different items in the LS might have to be modified for different ethnic groups | • 24-hour urinary copper excretion >100 μg/24 hours or 1,600 μg/24 hours after D-PCA challenge test | ||
| Tatsumi, 2011, Japan (51) | Retrospective cohort study of 23 pediatric and adult patients | • 10 patients had definitive ATP7B variants | Ceruloplasmin <10 mg/dL |
| • 9 of these patients had a Leipzig score >4 | |||
| Nicastro, 2010, Italy (21) | Case control study of 40 children with WD (26 boys and 14 girls, age range 1.1–20.9 years) and 58 age-matched and sex-matched patients with a liver disease other than WD | • Ceruloplasmin <20 mg/dL showed a sensitivity of 95% and a specificity of 84.5% | • Serum ceruloplasmin <20 mg/dL |
| • Urinary copper >40 lg/24 hours showed a sensitivity of 78.9% and a specificity of 87.9% | • Urinary copper >40 lg/24 hours | ||
| • Urinary copper values after penicillamine challenge did not significantly differ between WD patients and control subjects (sensitivity of 12%) | |||
| • The LS was proved to have positive and negative predictive values of 93% and 91.6%, respectively |
WD, Wilson Disease; LS, Leipzig Score; PPV, positive predictive value; NPV, negative predictive value.