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Long‐term follow‐up of 64 children with classical infantile‐onset Pompe disease since 2004: a French real‐life observational study

Title: Long‐term follow‐up of 64 children with classical infantile‐onset Pompe disease since 2004: a French real‐life observational study
Authors: Tardieu, M.; Cudejko, C.; Cano, A.; Hoebeke, C.; Bernoux, D.; Goetz, V.; Pichard, S.; Brassier, A.; Schiff, M.; Feillet, F.; Rollier, P.; Mention, K.; Dobbelaere, D.; Fouilhoux, A.; Espil-Taris, C.; Eyer, D.; Huet, F.; Walther-Louvier, U.; Barth, M.; Chevret, L.; Kuster, A.; Lefranc, J.; Neveu, J.; Pitelet, G.; Ropars, J.; Rivier, Francois; Roubertie, A.; Touati, G.; Vanhulle, C.; Tardieu, E.; Caillaud, C.; Froissart, R.; Champeaux, M.; Labarthe, F.; Chabrol, B.
Contributors: Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); Hôpital de la Timone CHU - APHM (TIMONE); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte CHU Necker (MaMEA Necker); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Necker - Enfants Malades AP-HP; Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL); Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois); Hôpital Sud CHU Rennes; Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Hôpital Jeanne de Flandre Lille; Hôpital Femme Mère Enfant CHU - HCL (HFME); Hospices Civils de Lyon (HCL); Hôpital Pellegrin; Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux)-Groupe hospitalier Pellegrin; Hôpital de Hautepierre Strasbourg; Hôpitaux Universitaires de Strasbourg (HUS); Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); Hôpital Gui de Chauliac CHU Montpellier; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Centre Hospitalier Universitaire d'Angers (CHU Angers); Centre hospitalier de Saint-Brieuc Hôpital Yves Le Foll (CH Saint-Brieuc); Groupement Hospitalier Territoire d'Armor (GHT Armor); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Physiopathologie des Adaptations Nutritionnelles (PhAN); Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Hôpital Morvan Brest; Hôpitaux Pédiatriques de Nice Lenval (CHU-Lenval); Centre Hospitalier Universitaire de Nice (CHU Nice); Physiologie & médecine expérimentale du Cœur et des Muscles U 1046 (PhyMedExp); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Institut des Neurosciences de Montpellier (INM); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Hôpital Charles Nicolle Rouen; CHU Rouen; Normandie Université (NU)-Normandie Université (NU); Université Lumière - Lyon 2 (UL2); Centre de Biologie et Pathologie Est Bron (CBPE); Niche, Nutrition, Cancer et métabolisme oxydatif (N2Cox); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Source: ISSN: 1351-5101.
Publisher Information: CCSD; Wiley
Publication Year: 2023
Collection: Université François-Rabelais de Tours: HAL
Subject Terms: enzyme replacement therapy; immunomodulation; infantile-onset Pompe disease; long-term outcomes; [SDV]Life Sciences [q-bio]
Description: International audience ; Background: Classical infantile-onset Pompe disease (IOPD) is the most severe form of Pompe disease. Enzyme replacement therapy (ERT) has significantly increased survival but only a few studies have reported long-term outcomes.Methods: We retrospectively analyzed the outcomes of classical IOPD patients diagnosed in France between 2004 and 2020.Results: Sixty-four patients were identified. At diagnosis (median age 4 months) all patients had cardiomyopathy and most had severe hypotonia (57 of 62 patients, 92%). ERT was initiated in 50 (78%) patients and stopped later due to being ineffective in 10 (21%). Thirty-seven (58%) patients died during follow-up, including all untreated and discontinued ERT patients, and 13 additional patients. Mortality was higher during the first 3 years of life and after the age of 12 years. Persistence of cardiomyopathy during follow-up and/or the presence of heart failure were highly associated with an increased risk of death. In contrast, cross-reactive immunologic material (CRIM)-negative status (n = 16, 26%) was unrelated to increased mortality, presumably because immunomodulation protocols prevent the emergence of high antibody titers to ERT. Besides survival, decreased ERT efficacy appeared after the age of 6 years, with a progressive decline in motor and pulmonary functions for most survivors.Conclusions: This study reports the long-term follow-up of one of the largest cohorts of classical IOPD patients and demonstrates high long-term mortality and morbidity rates with a secondary decline in muscular and respiratory functions. This decreased efficacy seems to be multifactorial, highlighting the importance of developing new therapeutic approaches targeting various aspects of pathogenesis.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/37235686; PUBMED: 37235686
DOI: 10.1111/ene.15894
Availability: https://hal.science/hal-04108445; https://hal.science/hal-04108445v1/document; https://hal.science/hal-04108445v1/file/2023%20Tardieu%20et%20al.,%20Long.pdf; https://doi.org/10.1111/ene.15894
Rights: https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.81255A6B
Database: BASE