Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community.
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 Information
Pedro Granjo: UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, Caparica, Portugal.
Carlota Pascoal: UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, Caparica, Portugal.
Diana Gallego: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
Rita Francisco: CDG & Allies-Professionals and Patient Associations International Network, Caparica, Portugal.
Jaak Jaeken: CDG & Allies-Professionals and Patient Associations International Network, Caparica, Portugal.
Tristen Moors: Glycomine, Inc, 733 Industrial Road, San Carlos, CA, 94070, USA.
Andrew C Edmondson: Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Kristin A Kantautas: Perlara PBC, Berkeley, CA, 94705, USA.
Mercedes Serrano: Neurology Department, Hospital Sant Joan de Déu, U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain.
Paula A Videira: UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, Caparica, Portugal. p.videira@fct.unl.pt.
Vanessa Dos Reis Ferreira: UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, Caparica, Portugal. sindromecdg@gmail.com. ORCID
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), and hypotonia in all studied CDG (V = 0.34, FDR = 7.0 × 10). 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.
