Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community

Abstract Background Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families’ a...

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Main Authors: Pedro Granjo, Carlota Pascoal, Diana Gallego, Rita Francisco, Jaak Jaeken, Tristen Moors, Andrew C. Edmondson, Kristin A. Kantautas, Mercedes Serrano, Paula A. Videira, Vanessa dos Reis Ferreira
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Orphanet Journal of Rare Diseases
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Online Access:https://doi.org/10.1186/s13023-024-03389-2
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author Pedro Granjo
Carlota Pascoal
Diana Gallego
Rita Francisco
Jaak Jaeken
Tristen Moors
Andrew C. Edmondson
Kristin A. Kantautas
Mercedes Serrano
Paula A. Videira
Vanessa dos Reis Ferreira
author_facet Pedro Granjo
Carlota Pascoal
Diana Gallego
Rita Francisco
Jaak Jaeken
Tristen Moors
Andrew C. Edmondson
Kristin A. Kantautas
Mercedes Serrano
Paula A. Videira
Vanessa dos Reis Ferreira
author_sort Pedro Granjo
collection DOAJ
description Abstract Background Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families’ and professionals’ experiences. Results and discussion A questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively. Analysis revealed the lack of seizures as a distinctive feature between PMM2-CDG (11.2%) with Other CDG (57.7%) at symptom onset. Hypotonia and developmental disability were prevalent symptoms across all studied CDG. Feeding problems were identified as an early onset symptom in PMM2-CDG (Cramer’s V (V) = 0.30, False Discovery Rate (FDR) = 3.8 × 10− 9), and hypotonia in all studied CDG (V = 0.34, FDR = 7.0 × 10− 3). The average time to diagnosis has decreased in recent years (now ~ 3.9 years), due to advancements namely the increased use of whole genome and exome sequencing. However, misdiagnoses remain prevalent (PMM2-CDG – 44.9%, non-PMM2-CDG – 64.8%). To address these challenges, we propose adapting medical training to increase awareness of CDG and other rare diseases, ongoing education for physicians, the development of educational resources for relevant medical units, and empowerment of families through patient organizations and support networks. Conclusion This study emphasizes the crucial role of community-centered research, and the insights families can offer to enhance CDG management. By pinpointing existing gaps and needs, our findings can inform targeted interventions and support systems to improve the lives of those impacted by CDG.
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spelling doaj-art-3cdd2f60fd6f4e29b8ff4316b5846dbb2025-08-20T02:18:33ZengBMCOrphanet Journal of Rare Diseases1750-11722024-11-0119111710.1186/s13023-024-03389-2Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the communityPedro Granjo0Carlota Pascoal1Diana Gallego2Rita Francisco3Jaak Jaeken4Tristen Moors5Andrew C. Edmondson6Kristin A. Kantautas7Mercedes Serrano8Paula A. Videira9Vanessa dos Reis Ferreira10UCIBIO – Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de LisboaUCIBIO – Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de LisboaCentro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de MadridCDG & Allies-Professionals and Patient Associations International NetworkCDG & Allies-Professionals and Patient Associations International NetworkGlycomine, IncDivision of Human Genetics, Department of Pediatrics, Children’s Hospital of PhiladelphiaPerlara PBCNeurology Department, Hospital Sant Joan de Déu, U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos IIIUCIBIO – Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de LisboaUCIBIO – Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de LisboaAbstract Background Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families’ and professionals’ experiences. Results and discussion A questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively. Analysis revealed the lack of seizures as a distinctive feature between PMM2-CDG (11.2%) with Other CDG (57.7%) at symptom onset. Hypotonia and developmental disability were prevalent symptoms across all studied CDG. Feeding problems were identified as an early onset symptom in PMM2-CDG (Cramer’s V (V) = 0.30, False Discovery Rate (FDR) = 3.8 × 10− 9), and hypotonia in all studied CDG (V = 0.34, FDR = 7.0 × 10− 3). The average time to diagnosis has decreased in recent years (now ~ 3.9 years), due to advancements namely the increased use of whole genome and exome sequencing. However, misdiagnoses remain prevalent (PMM2-CDG – 44.9%, non-PMM2-CDG – 64.8%). To address these challenges, we propose adapting medical training to increase awareness of CDG and other rare diseases, ongoing education for physicians, the development of educational resources for relevant medical units, and empowerment of families through patient organizations and support networks. Conclusion This study emphasizes the crucial role of community-centered research, and the insights families can offer to enhance CDG management. By pinpointing existing gaps and needs, our findings can inform targeted interventions and support systems to improve the lives of those impacted by CDG.https://doi.org/10.1186/s13023-024-03389-2Congenital disorders of glycosylation (CDG)Patient journeyDiagnostic odyssey journeyCommunity-centered researchRare diseases
spellingShingle Pedro Granjo
Carlota Pascoal
Diana Gallego
Rita Francisco
Jaak Jaeken
Tristen Moors
Andrew C. Edmondson
Kristin A. Kantautas
Mercedes Serrano
Paula A. Videira
Vanessa dos Reis Ferreira
Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
Orphanet Journal of Rare Diseases
Congenital disorders of glycosylation (CDG)
Patient journey
Diagnostic odyssey journey
Community-centered research
Rare diseases
title Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
title_full Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
title_fullStr Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
title_full_unstemmed Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
title_short Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
title_sort mapping the diagnostic odyssey of congenital disorders of glycosylation cdg insights from the community
topic Congenital disorders of glycosylation (CDG)
Patient journey
Diagnostic odyssey journey
Community-centered research
Rare diseases
url https://doi.org/10.1186/s13023-024-03389-2
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