Pediatric Wilson's Disease: Phenotypic, Genetic Characterization and Outcome of 182 Children in France.

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.

• Authors: Eduardo Couchonnal, Laurence Lion-François, Olivier Guillaud, Dalila Habes, Dominique Debray, Thierry Lamireau, Pierre Broué, Alexandre Fabre, Claire Vanlemmens, Rodolphe Sobesky, Frederic Gottrand, Laure Bridoux-Henno, Jérôme Dumortier, Abdelouahed Belmalih, Aurelia Poujois, Emmanuel Jacquemin, Anne Sophie Brunet, Muriel Bost, Alain Lachaux
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 73 Issue 4 Pg. e80-e86 (10 01 2021) ISSN: 1536-4801 [Electronic] United States
• PMID: 34091542 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Chemical References

• Copper
• Penicillamine

Topics

• Adolescent
• Child
• Child, Preschool
• Copper
• France (epidemiology)
• Hepatolenticular Degeneration (diagnosis, genetics, therapy)
• Humans
• Infant
• Penicillamine (therapeutic use)
• Retrospective Studies
• Treatment Outcome