Congenital disorders of glycosylation

Authors

  • Ana Raquel Mendes Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto https://orcid.org/0000-0002-8310-2525
  • Dulce Quelhas Genetic Biochemistry Unit, Centro de Genética Médica, Centro Hospitalar Universitário do Porto
  • Joana Correia Inborn Errors of Metabolism Unit, Department of Pediatrics, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto
  • Margarida Paiva Coelho Inborn Errors of Metabolism Unit, Pediatrics Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto https://orcid.org/0000-0002-6471-4067
  • Anabela Bandeira Inborn Errors of Metabolism Unit, Pediatrics Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto https://orcid.org/0000-0003-1203-8180
  • Esmeralda Martins Inborn Errors of Metabolism Unit, Pediatrics Department, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto

DOI:

https://doi.org/10.25753/BirthGrowthMJ.v31.i1.26341

Keywords:

congenital disorders of glycosylation, MPI-CDG, multisystemic disease, oral mannose, PMM2-CDG, serum transferrin isoelectric focusing

Abstract

Congenital disorders of glycosylation are a highly variable, rapidly expanding family of genetic diseases that result from defects in the synthesis of glycans. The vast majority of these monogenic diseases are inherited in an autosomal recessive way, but some types follow an autosomal dominant or X-linked inheritance.

The present work aimed to review the state of the art of congenital disorders of glycosylation, including available therapeutic options, and present a simplified diagnostic approach to this group of diseases.

Congenital disorders of glycosylation can be classified into four categories: N-linked glycosylation defects, O-linked glycosylation defects, combined glycosylation defects, and glycosphingolipid and glycosylphosphatidylinositol anchor synthesis defects. The phenotype may range from mild to severe, depending on disease severity. Clinical features include dysmorphic features, neurologic, dermatologic, cardiac, endocrine, immunologic, hematologic, gastrointestinal and liver involvement, and skeletal muscle abnormalities. As there is no universal or pathognomonic sign or symptom and no sensitive diagnostic test, it is of foremost importance to keep a high index of suspicion of these diseases. When a congenital disorder of glycosylation is suspected, the first step in screening is to perform serum transferrin isoelectric focusing. Molecular genetic testing is the most specific diagnostic test. Treatment is usually symptomatic, with specific treatment only available for some of these disorders.

Since congenital defects of glycosylation may affect any organ at any age and have variable clinical presentation, they should be considered in the differential diagnosis of any patient with multiorgan involvement.

Downloads

Download data is not yet available.

References

Vilarinho L, Quelhas D, Leão Teles E. Defectos congénitos de la glicosilación. In: Sanjurjo P, Baldellou A. editors. Diagnóstico y Tratamiento de las enfermedadas metabólicas hereditárias. 3ª edicion. Majadahonda (Madrid): Ergon; 2010. p. 921-35.

Chang IJ, He M, Lam CT. Congenital disorders of glycosylation. Ann Transl Med 2018; 6(24): 477.

Jaeken, J. Congenital disorders of glycosylation: A multi-genetic disease family with multiple subcellular locations. Journal of Mother and Child 2020; 24(2): 14-20.

Grünewald S, Matthijs G, Jaeken J. Congenital Disorders of Glycosylation: A Review. Pediatric Research 2002; 52(5): 618-24.

Cuddapah S, Ganetzky R. Neonatal Presentation of Congenital Disorders of Glycosylation. NeoReviews 2017; 18(4): 234-9.

Schiff M, Roda C, Monin M-L, Arion A, Barth M, Bednarek N et al. Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2- congenital disorder of glycosylation) and review of the literature. J Med Genet 2017; 54(12): 843-51.

Jaeken J, Matthijs G. Congenital Disorders of Glycosylation: A Rapidly Expanding Disease Family. Annu. Rev. Genomics Hum. Genet. 2007; 8: 261-78.

Ganetzky R, Reynoso FJ, He M. Congenital disorders of glycosylation. December 2017. (Assessed November 13, 2021). Available at https://www.sciencedirect.com/science/article/pii/B9780128028964000146?via%3Dihub.

Schjoldager KT, Narimatsu Y, Joshi HJ, Clausen H. Global view of human protein glycosylation pathways and functions. Nature Reviews Molecular Cell Biology 2020; 21(12): 729–49.

Jaeken J, Hennet T, Matthijs G, Freeze HH. CDG nomenclature: time for a change! Biochim Biophys Acta 2009; 1792(9): 825-6.

Verheijen J, Tahata S, Kozicz T, Witters P, Morava E. Therapeutic approaches in Congenital Disorders of Glycosylation (CDG) involving N-linked glycosylation: an update. Genetics in Medicine 2020; 22(2): 268-79.

Lipinski P, Tylki-Szymariska A. Congenital Disorders of Glycosylation: What Clinicians Need to Know? Front. Pediatr. 2021: 3(9): 715- 51.

Ferreira CR, Altassan R, Marques-Da-Silva D, Francisco R, Jaeken J, Morava E. Recognizable phenotypes in CDG. J Inherit Metab Dis. 2018; 41(3): 541-53.

Makhamreh MM, Cottingham N, Ferreira CR, Berger S, Al-Kouatly HB. Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review. J Inherit Metab Dis. 2020; 43(2): 223-33.

Rymen D, Jaeken J. Skin manifestations in CDG. J Inherit Metab Dis. 2014; 37(5): 699-708.

Paprocka J, Jezela-Stanek A, Tylki-Szymanska A, Grunewald S. Congenital Disorders of Glycosylation from a Neurological Perspective. Brain Sci. 2021; 1(11): 88.

Marques-da-Silva D, dos Reis Ferreira V, Monticelli M, Janeiro P, Videira PA, Witters P et al. Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. J Inherit Metab Dis 2017; 40(2): 195-207.

Houdou M, Foulquier F. Anomalies congénitales de la glycosylation (CDG). Médecine/sciences 2020; 36(8): 735-46.

Sosicka P, Ng BG, Freeze HH. Chemical Therapies for Congenital Disorders of Glycosylation. ACS Chem Biol 2021.

Sparks SE, Krasnewich DM. Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview. January, 2017. (Assessed November 13, 2021). Available at: https://www.ncbi.nlm.nih.gov/books/NBK1332.

Brasil S, Pascoal C, Francisco R, Marques-da-Silva D, Andreotti G, Videira PA, et al. CDG Therapies: From Bench to Bedside. Int. J. Mol. Sci. 2018; 19(5): 1304.

Grünewald S. Congenital disorders of glycosylation: rapidly enlarging group of (neuro)metabolic disorders. Early Hum Dev 2007; 83(12): 825-30.

Francisco R, Marques-da-Silva D, Brasil S, Pascoal C, dos Reis Ferreira V, Morava E, Jaeken J. The challenge of CDG diagnosis. Mol Genet Metab. 2019; 126(1): 1-5.

Quelhas D, Martins E, Azevedo L, Bandeira A, Diogo L, Garcia P et al. Congenital Disorders of Glycosylation in Portugal- Two Decades of Experience. The Journal of Pediatrics 2021; 231: 148-56.

Downloads

Published

2022-04-04

How to Cite

1.
Mendes AR, Quelhas D, Correia J, Paiva Coelho M, Bandeira A, Martins E. Congenital disorders of glycosylation. REVNEC [Internet]. 2022Apr.4 [cited 2024Mar.28];31(1):38-54. Available from: https://revistas.rcaap.pt/nascercrescer/article/view/26341

Issue

Section

Review Articles

Most read articles by the same author(s)

<< < 1 2