Author information

• ¹Hospices Civils de Lyon. National Center for Wilson's disease and Department of pediatric gastroenterology, hepatology and nutrition children's hospital of Lyon, France Claude Bernard Lyon 1 university Lyon, France Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Biliary Atresia and Genetic Cholestasis, FILFOIE, ERN RARE LIVER, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre, France Competence centre for Wilson disease Pediatric Hepatology Unit, Reference Center for Biliary Atresia and Genetic cholestasis, Hôpital Necker-Enfants Malades, AP-HP, Université Paris Centre, Paris, France. Children's Hospital, Paediatric Gastroenterology Unit, Bordeaux, France, Children University Hospital, Metabolic Disease Department, Toulouse, France, APH, Timone Enfant, Service de pédiatrie multidisciplinaire, Marseille, France, Aix Marseille Univ, INSERM, MMG ; Marseille, France, University Hospital of Besancon, Paediatric Gastroenterology Unit, Besacon, France, Paul Brousse Hospital, Hepatobiliary Centre, Hepatobiliary Centre, France, Univ- Lille, CHU Lille, UMR1286 Department of Pediatric Gastroenterology Hepatology and Nutrition, Lille, France, CHU Rennes, Department of Pediatric Gastroenterology, Rennes, France Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Lyon, France French National Rare Disease Reference Centre "Wilson's disease and other copper-related rare diseases", Rothschild Foundation Hospital, Neurology Department, Paris, France Inserm U1193, Hepatinov, University of Paris Saclay, Orsay, France;.

Abstract

Objectives: To describe a cohort of Wilson's disease (WD) paediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome.

Methods: Clinical data of 182 paediatric patients included in the French WD national registry from 01/03/1995 to 01/06/2019 were gathered.

Results: Diagnosis of WD was made at a mean age of 10.7 ± 4.2 years (range 1-18 years). At diagnosis, 154 patients (84.6%) had hepatic manifestations, 19 (10.4%) had neurological manifestations, and 9 patients (4.9%) were asymptomatic. The p.His1069Gln mutation was the most frequently encountered (14% of patients).Neurological patients were diagnosed at least one year after they presented their first symptoms. At diagnosis, the median urinary copper excretion (UCE) was 4.2 μmol/24 hours (0.2-253). The first-line treatment was D-penicillamine (DP) for 131 (72%) patients, zinc salts for 24 (13%) patients, and Trientine for 17 (9%) patients. Liver transplantation was performed in 39 (21.4%) patients, for hepatic indications in 33/39 patients or for neurological deterioration in 6/39 patients, mean UWDRS of the latter went from 90 ± 23.1 before LT to 26.8 ± 14.1 (p < 0.01) after a mean follow-up of 4.3 ± 2.5 years. Overall survival rate at 20 years of follow-up was 98%, patient and transplant-free combined survival was 84% at 20 years.

Conclusion: Diagnosis of WD can be challenging in children, particularly at early stages of liver disease and in case of neurological presentation; hence the support of clinical scores and genetic testing is essential. Diagnosis at early stages and proper treatment ensure excellent outcomes, subject to good long-term treatment compliance. LT is a valid option for end-stage liver disease not responding to treatment and can be discussed for selected cases of neurological deterioration.