RaDiCo-MPS - Mucopolysaccharidosis patients in France in the era of specific therapeutics FRESH-PEF74146-en Sonia GUEGUEN RaDiCo-MPS - Mucopolysaccharidosis patients in France in the era of specific therapeutics RaDiCo-MPS FRESH-PEF74146-en FRESH-PEF74146 C16-53 NCT06036693 14293 DC-2015-2482 Kumaran DEIVA INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) Epidemiology France Portal (PEF) AGENCE NATIONALE DE LA RECHERCHE (ANR) MINISTERE DE L’ENSEIGNEMENT SUPERIEUR, DE LA RECHERCHE ET DE L’ESPACE null Juliette;CARTON CPP CNIL Other Rare Diseases MPS Genetics Lysosomal disease Quality of Life Cohort Anaesthesiology Andrology and urology Cardiology and vascular medicine Dentistry Dermatology Gastroenterology Hematology Hepatology Medical genetics Neurology Ophthalmology Orthopaedics and traumatology Otolaryngology Paediatrics Physical and Rehabilitation Medicine Psychiatry Public, environmental and occupational health Pulmonary medicine Radiology and nuclear medicine Rheumatology Transplantation Mucopolysaccharidosis Socio-demographic and economic determinants Socio-demographic and economic determinants: Employment Socio-demographic and economic determinants: Education level Socio-demographic and economic determinants: Family situation Socio-demographic and economic determinants: Age Biological determinants Biological determinants: Genetic predisposition Biological determinants: Sex The primary objective of the MPS cohort is to characterize the epidemiology and natural history of mucopolysaccharidoses (MPS) by compiling a retrospective and prospective collection of detailed phenotypic data from French patients affected by these conditions. Secondary objectives include conducting an in-depth assessment of the overall benefit of current treatments—including their impact on quality of life—and establishing genotype-phenotype correlations for each type of MPS. Finally, the exploratory objective is to contribute to the identification of new, relevant biomarkers for future clinical trials, by establishing a list of biomarkers useful for therapeutic management and the improvement of patient monitoring. The RaDiCo-MPS cohort is a national, multicenter, non-interventional, observational, longitudinal, descriptive, retrospective, and prospective study sponsored by Inserm and coordinated by the RaDiCo platform. It involves pediatric and adult patients with mucopolysaccharidosis (MPS) who are followed in the French network of Reference and Competence Centers for Lysosomal and Inherited Metabolic Diseases (G2M network), consisting of 8 Reference Centers and 3 Competence Centers. The enrollment period is set at 9 years, extended through June 2027, and each enrolled patient will be followed for 5 years, bringing the total duration of the study to 16 years and 6 months, with follow-up scheduled through June 2032. MPS are rare lysosomal storage disorders caused by the accumulation of glycosaminoglycans in lysosomes, leading to progressive multiorgan involvement. Seven clinical subtypes have been identified (MPS I through IV, VI, VII, and IX), in addition to multiple sulfatase deficiency. Their overall incidence is estimated to be between 1 in 25,000 and 1 in 30,000 births. These are chronic, progressive diseases involving skeletal, visceral, ENT, cardiac, respiratory, and sometimes neurocognitive involvement, with severity varying greatly depending on the subtype. The advent of specific treatments (enzyme replacement therapy, hematopoietic stem cell transplantation) has altered the prognosis, although their overall benefit on quality of life and their cost-effectiveness have not yet been fully evaluated. The study population includes prevalent patients—those diagnosed since 1973 and still under follow-up in France—and incident patients diagnosed during the study. Approximately 950 patients were diagnosed between 1973 and 2013, half of whom are believed to still be alive; a total of approximately 500 patients are expected to be included in the cohort. The diagnosis is based on a significant enzyme deficiency associated with abnormal urinary excretion of glycosaminoglycans, supplemented by mutation analysis. There are no exclusion criteria. Data from deceased patients may be collected, unless the patient or their legal representatives expressly objected during the patient’s lifetime. Patients are identified and recruited through the G2M network, as well as with the assistance of French laboratories specializing in the diagnosis of metabolic diseases and patient organizations. The study does not alter the usual course of care and does not require any additional tests; however, it does involve the collection of additional biological samples (plasma and urine) at enrollment and then annually while on treatment. The cohort combines retrospective data—drawn from medical records and existing databases—with prospective data collected via the RaDiCo-MPS eCRF during routine follow-up visits, which occur one to four times a year depending on the patient’s age and disease progression. The data collected include clinical characteristics (growth, signs, complications by system, psychomotor and cognitive development), radiological, electrophysiological, biochemical (urinary GAGs, enzyme activities, specific antibodies), and molecular data, as well as questionnaires on quality of life and global impression of change (CGI-I, PGI-I), and medical-social questionnaires. The analyses will be primarily descriptive, illustrated by appropriate graphical representations, including calculations of means and standard deviations or percentages and confidence intervals, by visit and over the entire duration of the study, according to MPS subgroups. Comparative tests (ANOVA, chi-square, Fisher’s exact test) and Kaplan-Meier survival curves with the log-rank test will be used. Explanatory multivariate analyses (PCA, CDA, logistic regression) will be used to examine associations between treatments and patient outcomes, between phenotype and genotype, and between candidate biomarkers and therapeutic response. The health economic evaluation of healthcare costs will be the subject of a subsequent protocol amendment. The RaDiCo-MPS cohort thus constitutes a structured database of clinical, biological, genetic, and quality-of-life data collected over the long term from a nationally coordinated network of expert centers, enabling a better characterization of the natural history and management of mucopolysaccharidoses in France. France Auvergne Rhône-Alpes Bretagne Centre-Val de Loire Grand Est Hauts-de-France Ile-de-France Normandie Nouvelle-Aquitaine Occitanie Pays de la Loire Provence - Alpes - Côte d'Azur Individus Patients population Female Male Infant, Newborn (birth to 28 days) Infant (28 days to 2 years) Child, Preschool (2 to 5 years) Child (6 to 12 years) Adolescent (13 to 18 years) Young Adult (19 to 24 years) Adult (25 to 44 years) Middle Aged (45 to 64 years) The RaDiCo-MPS Cohort inclusion criteria are the following: • A clinically relevant enzyme deficiency, with abnormally elevated urinary GAG excretion - And/or identification of pathogenic mutations . • Signed informed consent or parents/guardian non-opposition for deceased patients (minor or protected major) There are no non-inclusion criteria. Clinical data Paraclinical data (non-biological) Paraclinical data (non-biological) : Imaging Paraclinical data (non-biological) : Anthropometry Paraclinical data (non-biological) : Function testing Biological data Environmental / exposure data Genetic / genomic data Participant-reported health data Clinical and phenotypic data are structured using appropriate medical thesauri and nomenclatures notably Orphanet and HPO in order to allow consistent coding and better structuring of the data collected. Steering Committee: Bénédicte HERON, Samia PICHARD, Anais BRASSIER, François FEILLET, Elise SACAZE Scientific Committee: Bénédicte HERON, Anais BRASSIER, Catherine CAILLAUD, Samia PICHARD, Elise SACAZE, Anne-Sophie GUEMANN, François FEILLET, Elise JEANNESSON, Magali GORCE, Delphine GENEVAZ, the RaDiCo Project Team + Sonia GUEGUEN Data quality is ensured under the Data Management Plan and the Data Validation Plan with continuous data management. Data collected in the eCRF undergo consistency and completeness checks in particular through automatic control rules and a query system. Checks are carried out to identify data that are missing inconsistent or require clarification from the investigating centres. Corrections are made after verification with the centres concerned in accordance with research data management procedures. Data management process flowcharts are also used to document the data processing and validation circuits the various quality control points and the responsibilities of those involved at each stage. The primary endpoint is the long-term course of the clinical, biological and paraclinical characteristics of patients with mucopolysaccharidosis (MPS), in particular type IVA patients treated with elosulfase alfa. This course will be assessed from clinical data (growth, signs, symptoms, complications, psychomotor development, cognitive functions and disability), radiological, electrophysiological, biochemical and molecular data. Data will be collected at inclusion, then annually during follow-up, and supplemented retrospectively for some data from medical records for patients already diagnosed. The secondary endpoints are designed to assess the long-term course of patients with mucopolysaccharidosis (MPS) type IVA who have discontinued treatment with elosulfase alfa or who have never received this treatment. They include a description of the management and course of the disease before and in the absence of specific treatment, as well as during treatment, based on medical and functional data, appropriate scales and questionnaires, quality-of-life measures, the Clinician’s Global Impression of Improvement (CGI-I) and Patient’s Global Impression of Improvement (PGI-I), as well as life expectancy. The study also aims to identify genetic mutations and establish genotype-phenotype relationships for each type of MPS. Other Data is collected annually for 5 years per patient. Complete enumeration (including consecutive recruitment) Through organizations (health services or institutions schools businesses etc.) < 500 individuals Converting or copying information into a structured record Interview with the participant (including clinical) Measurements and tests Physical/biological measurements (blood pressure, weight, biochemistry, imaging, etc.) Psychological tests/clinical scales (depression, cognition, quality of life, etc.) Observation (clinical or behavioural) Recording (audio, video, electrophysiological, imaging) Self-administered questionnaire Observational Study Observational Study Cohort study Monitoring by participant visit to the investigation center 310 patients au 01/10/2026 Ongoing study The data is hosted in France, within the secure France Cohortes data repository, by a hosting provider certified as a Health Data Host (HDS). It is collected and centralized in a secure eCRF, accessible only to duly authorized individuals in accordance with current security and access management procedures. Restricted access The available data files consist of data collected as part of the cohort and selected based on the purpose of the access request. Certain collected data may not be included in the files provided if they are subject to regulatory, ethical, or personal data protection restrictions. Access to information regarding the cohort is contingent upon compliance with the confidentiality obligations applicable to the data, documents, and information made available. Authorized users agree to use this information solely for the approved purposes and not to disclose it to unauthorized third parties. These obligations may be formalized in specific agreements or contracts governing access to the data. Access to the dataset is governed by an access request procedure. Data access takes place exclusively within the France Cohortes secure environment, with no possibility of extracting raw data to an external environment. The data are not freely distributed, and their use is limited to authorized research projects in accordance with the cohort’s governance rules. Users must comply with the access conditions, confidentiality agreements, personal data protection rules, and data utilization guidelines established by the cohort. Juliette;CARTON Prior to any publication, the SRP Lead—in consultation with the SRP Manager, if applicable—shall determine, by mutual agreement with the relevant project committee and based on each individual’s respective intellectual contributions, the order of authorship and the number of authors from each entity participating in the project. Publications must include at least one author from the Sponsor among their authors. Provided that this practice is accepted by the publishers of these scientific publications, RaDiCo will be listed as a co-author of the publication. In the event of refusal by the publisher, the members of the RaDiCo Consortium Agreement will provide the SRP Manager or the SRP Lead with the list of co-authors. Before publication, articles must be submitted to the relevant Project committee for review. Users who wish to publish must take into account all comments made by the relevant committee, provided that such comments are well-founded and not arbitrary. The terms and conditions for publication and dissemination are specified in the SRP Agreement. According to the cohort’s Resource Access Charter, requests must be submitted as a research project synopsis to mps@radico.fr (reviewed within one month by the RaDiCo-MPS Scientific Committee). Requests for access to RaDiCo-MPS data (aggregated or individual) will be reviewed by the Scientific Committee following submission of a Specific Research Project (SRP) summary, as defined in the Resource Access Charter. Data access is restricted to specific research projects (SRP). Any data access request is submitted by a user and assessed by the cohort’s relevant bodies, including a scientific review by the Scientific Committee and a feasibility, regulatory and legal analysis by the teams concerned. Once approved by the relevant bodies, the terms of data access and use are set out in a specific agreement. Results from the projects may be disseminated as scientific publications, presentations or reports, in compliance with confidentiality and the regulations applicable to health data.