Why do we want to learn about the Epidemiology in CDG?

  • CDG Clinical trials are emerging!  One of the great challenges for CDG clinical trials is the availability of the population living with CDG! For example, by knowing the exact number of CDG population clinical trials can be appropriately designed and set up as we can better determine the need for multicountry and multicenter involvement. Among many other advantages.
  • It is then of great importance understanding the true number of individuals with CDG to boost drug development, and successfully advance and access CDG treatments!

Which are the challenges around Epidemiology in CDG?

Even though through the years there has been some studies on the epidemiology of CDG, so far, no review of literature was done, with the main key-points that difficult the epidemiological study of CDG being:

  1. The information is scattered, not just for the reported epidemiologic evidence being a “side finding” and not being exactly the scope of the investigation; but also, the few epidemiological studies being targeted at specific populations and CDG types.
  2. Several patients were followed in different cohort studies done by different institutes, so repeated patients contribute for the lack of reliable information on this topic.
  3. Following the previous point, biochemical and genetic samples from different patients were used in different studies.
  4. Studies on allelic frequency are done with a small sample of patients, that may not represent well their group (for example, studies with a small number of PMM2-CDG patients, the most common CDG type, with over 1000 diagnosed patients worldwide).
  5. Only a few countries, most of them European, have done epidemiologic studies for CDG in their population, so research evidence on this subject is scarce.
  6. Many cases may still stay undiagnosed. 

Ergo, we extracted information on epidemiology from several sources and gathered it here, with the scope of contributing to the study of Epidemiology on CDG and to identify the gaps that are preventing the progress regarding this topic. 

  • Exact prevalence rate is difficult to obtain 
  • Low level of consistency between studies
  • Poor documentation of methods used- 
  • Confusion between incidence and prevalence 
  • Confusion between incidence at birth and lifelong incidence

CDG around the world

We recommend the following articles, as they cover the prevalence of CDG across various populations. If you have any problem trying to access them, we can concede them to you, if you contact us by filling the following CONTACT FORM

  • Pajusalu, S., Vals, M. A., Mihkla, L., Šamarina, U., Kahre, T., & Õunap, K. (2021). The Estimated Prevalence of N-Linked Congenital Disorders of Glycosylation Across Various Populations Based on Allele Frequencies in General Population Databases. Frontiers in genetics, 12, 719437. https://doi.org/10.3389/fgene.2021.719437
  • Schollen, E., Kjaergaard, S., Legius, E. et al. Lack of Hardy-Weinberg equilibrium for the most prevalent PMM2 mutation in CDG-Ia (congenital disorders of glycosylation type Ia). Eur J Hum Genet 8, 367–371 (2000). https://doi.org/10.1038/sj.ejhg.5200470
  • Péanne, R., de Lonlay, P., Foulquier, F., Kornak, U., Lefeber, D. J., Morava, E., Pérez, B., Seta, N., Thiel, C., Van Schaftingen, E., Matthijs, G., & Jaeken, J. (2018). Congenital disorders of glycosylation (CDG): Quo vadis?. European journal of medical genetics, 61(11), 643–663. https://doi.org/10.1016/j.ejmg.2017.10.012


  • Freeze, H. H., Chong, J. X., Bamshad, M. J., & Ng, B. G. (2014). Solving glycosylation disorders: fundamental approaches reveal complicated pathways. American journal of human genetics, 94(2), 161–175. https://doi.org/10.1016/j.ajhg.2013.10.024
  • Wicklund, C. L., Pauli, R. M., Johnston, D., & Hecht, J. T. (1995). Natural history study of hereditary multiple exostoses. American journal of medical genetics, 55(1), 43–46. https://doi.org/10.1002/ajmg.1320550113


  • Delgado, M. A., Martinez-Domenech, G., Sarrión, P., Urreizti, R., Zecchini, L., Robledo, H. H., Segura, F., de Kremer, R. D., Balcells, S., Grinberg, D., & Asteggiano, C. G. (2014). A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG. Scientific reports, 4, 6407. https://doi.org/10.1038/srep06407


  • Barone, R., Carrozzi, M., Parini, R., Battini, R., Martinelli, D., Elia, M., Spada, M., Lilliu, F., Ciana, G., Burlina, A., Leuzzi, V., Leoni, M., Sturiale, L., Matthijs, G., Jaeken, J., Di Rocco, M., Garozzo, D., & Fiumara, A. (2015). A nationwide survey of PMM2-CDG in Italy: high frequency of a mild neurological variant associated with the L32R mutation. Journal of neurology, 262(1), 154–164. https://doi.org/10.1007/s00415-014-7549-7
  • Ciavarella, M., Coco, M., Baorda, F., Stanziale, P., Chetta, M., Bisceglia, L., Palumbo, P., Bengala, M., Raiteri, P., Silengo, M., Caldarini, C., Facchini, R., Lala, R., Cavaliere, M. L., De Brasi, D., Pasini, B., Zelante, L., Guarnieri, V., & D'Agruma, L. (2013). 20 novel point mutations and one large deletion in EXT1 and EXT2 genes: report of diagnostic screening in a large Italian cohort of patients affected by hereditary multiple exostosis. Gene, 515(2), 339–348. https://doi.org/10.1016/j.gene.2012.11.055


  • Yıldız Y, Arslan M, Çelik G, et al. Genotypes and estimated prevalence of phosphomannomutase 2 deficiency in Turkey differ significantly from those in Europe. Am J Med Genet A. 2020;182(4):705-712. https://doi.org/10.1002/ajmg.a.61488


  • Stancheva-Ivanova, M.K., Wuyts, W., van Hul, E., Radeva, B.I., Vazharova, R.V., Sokolov, T.P., Vladimirov, B.Y., Apostolova, M.D. and Kremensky, I.M. (2011), Clinical and molecular studies of EXT1/EXT2 in Bulgaria. J Inherit Metab Dis, 34: 917-921. https://doi.org/10.1007/s10545-011-9314-8


  • Goreta, S. S., Dabelic, S., & Dumic, J. (2011). Employment of single-strand conformation polymorphism analysis in screening for α-1,3 glucosyltransferase gene mutation A333V in Croatian population. Journal of clinical laboratory analysis, 25(2), 65–70. https://doi.org/10.1002/jcla.20425


  • Lipiński, P., Bogdańska, A., & Tylki-Szymańska, A. (2021). Congenital disorders of glycosylation: Prevalence, incidence and mutational spectrum in the Polish population. Molecular Genetics and Metabolism Reports, 27, 100726. https://doi.org/10.1016/j.ymgmr.2021.100726
  • Jamsheer, A., Socha, M., Sowińska-Seidler, A., Telega, K., Trzeciak, T., & Latos-Bieleńska, A. (2014). Mutational screening of EXT1 and EXT2 genes in Polish patients with hereditary multiple exostoses. Journal of applied genetics, 55(2), 183–188. https://doi.org/10.1007/s13353-014-0195-z


  • Briones, P., Vilaseca, M. A., Schollen, E., Ferrer, I., Maties, M., Busquets, C., Artuch, R., Gort, L., Marco, M., van Schaftingen, E., Matthijs, G., Jaeken, J., & Chabás, A. (2002). Biochemical and molecular studies in 26 Spanish patients with congenital disorder of glycosylation type Ia. Journal of inherited metabolic disease, 25(8), 635–646. https://doi.org/10.1023/a:1022825113506
  • Pérez-Dueñas, B., García-Cazorla, A., Pineda, M., Poo, P., Campistol, J., Cusí, V., Schollen, E., Matthijs, G., Grunewald, S., Briones, P., Pérez-Cerdá, C., Artuch, R., & Vilaseca, M. A. (2009). Long-term evolution of eight Spanish patients with CDG type Ia: typical and atypical manifestations. European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society, 13(5), 444–451. https://doi.org/10.1016/j.ejpn.2008.09.002

Saudi Arabia

  • Alsubhi, S., Alhashem, A., Faqeih, E., Alfadhel, M., Alfaifi, A., Altuwaijri, W., Alsahli, S., Aldhalaan, H., Alkuraya, F. S., Hundallah, K., Mahmoud, A., Alasmari, A., Mutairi, F. Al, Abduraouf, H., AlRasheed, L., Alshahwan, S., & Tabarki, B. (2017). Congenital disorders of glycosylation: The Saudi experience. American Journal of Medical Genetics Part A, 173(10), 2614–2621. https://doi.org/10.1002/ajmg.a.38358


  • Ishigaki, K., Ihara, C., Nakamura, H., Mori-Yoshimura, M., Maruo, K., Taniguchi-Ikeda, M., Kimura, E., Murakami, T., Sato, T., Toda, T., Kaiya, H., & Osawa, M. (2018). National registry of patients with Fukuyama congenital muscular dystrophy in Japan. Neuromuscular disorders : NMD, 28(10), 885–893. https://doi.org/10.1016/j.nmd.2018.08.001


  • Monin, M. L., Mignot, C., De Lonlay, P., Héron, B., Masurel, A., Mathieu-Dramard, M., Lenaerts, C., Thauvin, C., Gérard, M., Roze, E., Jacquette, A., Charles, P., de Baracé, C., Drouin-Garraud, V., Khau Van Kien, P., Cormier-Daire, V., Mayer, M., Ogier, H., Brice, A., Seta, N., … Héron, D. (2014). 29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype. Orphanet journal of rare diseases, 9, 207. https://doi.org/10.1186/s13023-014-0207-4
  • Schiff, M., Roda, C., Monin, M. L., Arion, A., Barth, M., Bednarek, N., Bidet, M., Bloch, C., Boddaert, N., Borgel, D., Brassier, A., Brice, A., Bruneel, A., Buissonnière, R., Chabrol, B., Chevalier, M. C., Cormier-Daire, V., De Barace, C., De Maistre, E., De Saint-Martin, A., … De Lonlay, P. (2017). 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. Journal of medical genetics, 54(12), 843–851. https://doi.org/10.1136/jmedgenet-2017-104903


  • Quelhas, D., Martins, E., Azevedo, L., Bandeira, A., Diogo, L., Garcia, P., Sequeira, S., Ferreira, A. C., Teles, E. L., Rodrigues, E., Fortuna, A. M., Mendonça, C., Fernandes, H. C., Medeira, A., Gaspar, A., Janeiro, P., Oliveira, A., Laranjeira, F., Ribeiro, I., Souche, E., … Jaeken, J. (2021). Congenital Disorders of Glycosylation in Portugal-Two Decades of Experience. The Journal of pediatrics, 231, 148–156. https://doi.org/10.1016/j.jpeds.2020.12.026


  • Vals, M. A., Pajusalu, S., Kals, M., Mägi, R., & Õunap, K. (2018). The Prevalence of PMM2-CDG in Estonia Based on Population Carrier Frequencies and Diagnosed Patients. JIMD reports, 39, 13–17. https://doi.org/10.1007/8904_2017_41

Scandinavian countries

  • Bjursell, C., Erlandson, A., Nordling, M., Nilsson, S., Wahlström, J., Stibler, H., Kristiansson, B., & Martinsson, T. (2000). PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families. Human Mutation, 16(5), 395–400. https://doi.org/10.1002/1098-1004(200011)16:5<395::AID-HUMU3>3.0.CO;2-T

Further reading

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2022 https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf

What solutions might boost knowledge on Epidemiology in CDG?

  1. A Literature review - full report and publication
  2. Infographic - For communication and dissemination
  3. Slidedeck - For research, awareness, educational and advocacy purposes within governmental, funding and related organisations

If you wish to know more about the epidemiology of CDG, the CDG&Allies-PPAIN team made a toolkit available for the community, consisting of a literature review regarding the published epidemiological data on CDG (which is expected to be published in 2022); an infographic, a powerpoint presentation and the recording of the session about epidemiology during the 5th World CDG Conference! If you wish to access the later three, you need to be registered in our platform (log in /create new account HERE). For further information, don’t hesitate to contact us! You just have to fill the contact form and explain how we can help you! 

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Ana Piedade, Sci and Volunteer Program 2021, NOVA School of Science and Technology, Portugal.


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