Francisco, RitaPascoal, CarlotaMarques-da-Silva, DorindaBrasil, SandraPimentel-Santos, Fernando MAltassan, RuqaiahJaeken, JaakGrosso, Ana RitaDos Reis Ferreira, VanessaVideira, Paula A2021-05-052021-05-052020-07-032077-0383PURE: 18996701PURE UUID: da2433c0-a1e2-4e11-9643-172506c4d24ePubMed: 32635232WOS: 000557887100001ORCID: /0000-0001-5987-2485/work/93369449ORCID: /0000-0001-6974-4209/work/93369553PubMedCentral: PMC7408855Scopus: 85092295900http://hdl.handle.net/10362/117131SFRH/BD/124326/2016 SFRH/BD/138647/2018Congenital disorders of glycosylation (CDG) are rare diseases with variable phenotypes and severity. Immunological involvement remains a largely uncharted topic in CDG, mainly due to lack of robust data. To better characterize immune-related manifestations' prevalence, relevance, and quality-of-life (QoL) impact, we developed electronic questionnaires targeting (1) CDG patients and (2) the general "healthy" population. Two-hundred and nine CDG patients/caregivers and 349 healthy participants were included in this study. PMM2-CDG was the most represented CDG (n = 122/209). About half of these participants (n = 65/122) described relevant infections with a noteworthy prevalence of those affecting the gastrointestinal tract (GI) (63.1%, n = 41/65). Infection burden and QoL impact were shown as infections correlated with more severe clinical phenotypes and with a set of relevant non-immune PMM2-CDG signs. Autoimmune diseases had only a marginal presence in PMM2-CDG (2.5%, n = 3/122), all being GI-related. Allergy prevalence was also low in PMM2-CDG (33%, n = 41/122) except for food allergies (26.8%, n = 11/41, of PMM2-CDG and 10.8%, n = 17/158, of controls). High vaccination compliance with greater perceived ineffectiveness (28.3%, n = 17/60) and more severe adverse reactions were described in PMM2-CDG. This people-centric approach not only confirmed literature findings, but created new insights into immunological involvement in CDG, namely by highlighting the possible link between the immune and GI systems in PMM2-CDG. Finally, our results emphasized the importance of patient/caregiver knowledge and raised several red flags about immunological management.3778388engcongenital disorder(s) of glycosylation (CDG)PMM2-CDGimmune responseinfectionsallergiesvaccinationgastrointestinal tract (GI)e-questionnairepeople-centricitySDG 3 - Good Health and Well-beingjournal article10.3390/jcm9072092