P0183 DIAGNOSIS AND OUTCOME OF WILSON DISEASE IN A PAEDIATRIC COHORT

Introduction: Wilson disease (WD) is highly variable clinically. It may present as hepatic, neurological or psychiatric disease. Classic features include: age at presentation between 5 and 35 years-old, Kayser-Fleischer (K-F) rings evident, and serum ceruloplasmin <50 mg/L. In non-classic cases diagnosis is difficult. With >250 mutations of the ATP7B gene identified and high prevalence of compound heterozygotes, genetic diagnosis—though definitive—may be elusive. The aim of this study was to review our clinical experience with WD at the Hospital for Sick Children in the past 20 years. Methods: 35 patients were reviewed who have been diagnosed or treated at the Hospital for Sick Children; adult and correspondence-only referral patients were excluded. Results: 5 patients presented with fulminant hepatic failure (FHF): 4 (3 female) had typical Wilsonian FHF and all required liver transplant (OLT). One male patient who had WD and coincidental viral FHF survived without OLT. Of the other 30 patients (15 F, 15 M), 22 presented with clinical disease (21 hepatic) and 8 were identified by sib screening. These 30 patients were young (mean age 10.8 ± 3.4 [SD] yrs). K-F rings were identified in 14 of 28 patients (50%); no statistically significant difference in age was found between those with or without K-F rings. Mean serum Cu concentration was 9.0 micromol/L (within normal range in 25%). Serum ceruloplasmin was <50 mg/L in 12 of 28 patients and >150 mg/L in 8 of 28 patients. Mean basal 24-hr urinary Cu (BUrCu; n=23) was 11.5 micromol/d. All but one patient (96%) had BUrCu >0.6 micromol/d; 7 patients had BUrCu 0.6–3 micromol/d. After pencillamine challenge, 9 of 16 patients had urinary Cu excretion of at least 25 micromol/d. Notably, 7 patients (44%) did not achieve this benchmark, but diagnosis was secure or genetically proven in all 7. In subset analysis (n= at least 15), liver biopsy rarely showed copper histochemically (positive in 24%) but often showed typical changes in mitochondria by electron microscopy (in 93%). The Nazer index (Gut 1986;27:1377) used in 14 patients was inaccurate in predicting outcome of 2 patients. Genotype determination frequently revealed Arg778Leu. Currently 29 of 35 patients are alive without OLT and 68% are taking either trientine or zinc. Conclusion: K-F rings are infrequently found in children with WD. Serum ceruloplasmin is often not informative. Basal 24-hr urinary Cu excretion is nearly always >0.6 micromol/d. Some WD patients may not have a “diagnostic” penicillamine challenge.

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