Pediatric Wilson's Disease
Phenotypic, Genetic Characterization and Outcome of 182 Children in France
Corresponding Author
Eduardo Couchonnal
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Address correspondence and reprint requests to Eduardo Couchonnal, Service de Gastroentérologie, Hépatologie et Nutrition, Hôpital Femme Mère Enfant, 59 boulevard Pinel, 69677 Bron cedex, France (e-mail: [email protected]).Search for more papers by this authorLaurence Lion-François
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorOlivier Guillaud
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorDalila Habes
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, Paris
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Search for more papers by this authorDominique Debray
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Pediatric Hepatology Unit, Reference Center for Biliary Atresia and Genetic cholestasis, Hôpital Necker-Enfants Malades, AP-HP, Université Paris Centre, Paris
Search for more papers by this authorThierry Lamireau
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Children's Hospital, Paediatric Gastroenterology Unit, Bordeaux
Search for more papers by this authorPierre Broué
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Children University Hospital, Metabolic Disease Department, Toulouse
Search for more papers by this authorAlexandre Fabre
Competence Centre for Wilson Disease, Université Paris Centre, Paris
APH, Timone Enfant, Service de pédiatrie multidisciplinaire, Marseille
Aix Marseille Univ, INSERM, MMG, Marseille
Search for more papers by this authorClaire Vanlemmens
Competence Centre for Wilson Disease, Université Paris Centre, Paris
University Hospital of Besancon, Paediatric Gastroenterology Unit, Besacon
Search for more papers by this authorRodolphe Sobesky
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Paul Brousse Hospital, Hepatobiliary Centre, Hepatobiliary Centre, Lille
Search for more papers by this authorFrederic Gottrand
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Univ-Lille, CHU Lille, UMR1286, Department of Pediatric Gastroenterology Hepatology and Nutrition, Lille
Search for more papers by this authorLaure Bridoux-Henno
Competence Centre for Wilson Disease, Université Paris Centre, Paris
CHU Rennes, Department of Pediatric Gastroenterology, Rennes
Search for more papers by this authorJérôme Dumortier
Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Lyon
Claude Bernard Lyon 1 University Lyon, Paris
Search for more papers by this authorAbdelouahed Belmalih
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorAurelia Poujois
French National Rare Disease Reference Centre “Wilson's disease and other copper-related rare diseases”, Rothschild Foundation Hospital, Neurology Department, Paris
Search for more papers by this authorEmmanuel Jacquemin
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, Paris
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Inserm U1193, Hepatinov, University of Paris Saclay, Orsay, France
Search for more papers by this authorAnne Sophie Brunet
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorMuriel Bost
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorAlain Lachaux
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Claude Bernard Lyon 1 University Lyon, Paris
Search for more papers by this authorCorresponding Author
Eduardo Couchonnal
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Address correspondence and reprint requests to Eduardo Couchonnal, Service de Gastroentérologie, Hépatologie et Nutrition, Hôpital Femme Mère Enfant, 59 boulevard Pinel, 69677 Bron cedex, France (e-mail: [email protected]).Search for more papers by this authorLaurence Lion-François
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorOlivier Guillaud
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorDalila Habes
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, Paris
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Search for more papers by this authorDominique Debray
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Pediatric Hepatology Unit, Reference Center for Biliary Atresia and Genetic cholestasis, Hôpital Necker-Enfants Malades, AP-HP, Université Paris Centre, Paris
Search for more papers by this authorThierry Lamireau
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Children's Hospital, Paediatric Gastroenterology Unit, Bordeaux
Search for more papers by this authorPierre Broué
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Children University Hospital, Metabolic Disease Department, Toulouse
Search for more papers by this authorAlexandre Fabre
Competence Centre for Wilson Disease, Université Paris Centre, Paris
APH, Timone Enfant, Service de pédiatrie multidisciplinaire, Marseille
Aix Marseille Univ, INSERM, MMG, Marseille
Search for more papers by this authorClaire Vanlemmens
Competence Centre for Wilson Disease, Université Paris Centre, Paris
University Hospital of Besancon, Paediatric Gastroenterology Unit, Besacon
Search for more papers by this authorRodolphe Sobesky
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Paul Brousse Hospital, Hepatobiliary Centre, Hepatobiliary Centre, Lille
Search for more papers by this authorFrederic Gottrand
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Univ-Lille, CHU Lille, UMR1286, Department of Pediatric Gastroenterology Hepatology and Nutrition, Lille
Search for more papers by this authorLaure Bridoux-Henno
Competence Centre for Wilson Disease, Université Paris Centre, Paris
CHU Rennes, Department of Pediatric Gastroenterology, Rennes
Search for more papers by this authorJérôme Dumortier
Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Lyon
Claude Bernard Lyon 1 University Lyon, Paris
Search for more papers by this authorAbdelouahed Belmalih
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorAurelia Poujois
French National Rare Disease Reference Centre “Wilson's disease and other copper-related rare diseases”, Rothschild Foundation Hospital, Neurology Department, Paris
Search for more papers by this authorEmmanuel Jacquemin
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, Paris
Competence Centre for Wilson Disease, Université Paris Centre, Paris
Inserm U1193, Hepatinov, University of Paris Saclay, Orsay, France
Search for more papers by this authorAnne Sophie Brunet
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorMuriel Bost
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Search for more papers by this authorAlain Lachaux
Hospices Civils de Lyon, National Center for Wilson's Disease and Department of Pediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon, Paris
Claude Bernard Lyon 1 University Lyon, Paris
Search for more papers by this authorThe authors report no conflicts of interest.
ABSTRACT
Objectives:
To describe a cohort of Wilson disease (WD) pediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome.
Methods:
Clinical data of 182 pediatric 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 1 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 of 39 patients or for neurological deterioration in 6 of 39 patients, mean Unified Wilson's Disease Rating Scale of the latter went from 90 ± 23.1 before liver transplantation (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 the 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.
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