Congenital Disorders of Glycosylation: What Clinicians Need to Know?

Overview

Journal Front Pediatr

Specialty Pediatrics

Date 2021 Sep 20

PMID 34540767

Citations 23

Authors

Patryk Lipinski

Anna Tylki-Szymanska

Affiliations

Soon will be listed here.

Abstract

Congenital disorders of glycosylation (CDG) are a group of clinically heterogeneous disorders characterized by defects in the synthesis of glycans and their attachment to proteins and lipids. This manuscript aims to provide a classification of the clinical presentation, diagnostic methods, and treatment of CDG based on the literature review and our own experience (referral center in Poland). A diagnostic algorithm for CDG was also proposed. Isoelectric focusing (IEF) of serum transferrin (Tf) is still the method of choice for diagnosing N-glycosylation disorders associated with sialic acid deficiency. Nowadays, high-performance liquid chromatography, capillary zone electrophoresis, and mass spectrometry techniques are used, although they are not routinely available. Since next-generation sequencing became more widely available, an improvement in diagnostics has been observed, with more patients and novel CDG subtypes being reported. Early and accurate diagnosis of CDG is crucial for timely implementation of appropriate therapies and improving clinical outcomes. However, causative treatment is available only for few CDG types.

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References

Brancaccio A . A molecular overview of the primary dystroglycanopathies. J Cell Mol Med. 2019; 23(5):3058-3062. PMC: 6484290. DOI: 10.1111/jcmm.14218. View

Helmus Y, Denecke J, Yakubenia S, Robinson P, Luhn K, Watson D . Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter. Blood. 2006; 107(10):3959-66. DOI: 10.1182/blood-2005-08-3334. View

Sassi A, Lazaroski S, Wu G, Haslam S, Fliegauf M, Mellouli F . Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J Allergy Clin Immunol. 2014; 133(5):1410-9, 1419.e1-13. PMC: 4825677. DOI: 10.1016/j.jaci.2014.02.025. View

Al-Maawali A, Miller E, Schulze A, Yoon G, Blaser S . Subcutaneous fat pads on body MRI--an early sign of congenital disorder of glycosylation PMM2-CDG (CDG1a). Pediatr Radiol. 2013; 44(2):222-5. DOI: 10.1007/s00247-013-2782-2. View

Bogdanska A, Lipinski P, Szymanska-Rozek P, Jezela-Stanek A, Rokicki D, Socha P . Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up. Orphanet J Rare Dis. 2021; 16(1):17. PMC: 7789416. DOI: 10.1186/s13023-020-01657-5. View

Vajro P, Zielinska K, Ng B, Maccarana M, Bengtson P, Poeta M . Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation. Orphanet J Rare Dis. 2018; 13(1):4. PMC: 5763540. DOI: 10.1186/s13023-017-0757-3. View

Marques-da-Silva D, Francisco R, Webster D, Dos Reis Ferreira V, Jaeken J, Pulinilkunnil T . Cardiac complications of congenital disorders of glycosylation (CDG): a systematic review of the literature. J Inherit Metab Dis. 2017; 40(5):657-672. DOI: 10.1007/s10545-017-0066-y. View

Chiyonobu T, Inoue N, Morimoto M, Kinoshita T, Murakami Y . Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation syndrome. J Med Genet. 2013; 51(3):203-7. DOI: 10.1136/jmedgenet-2013-102156. View

Bogdanska A, Lipinski P, Szymanska-Rozek P, Jankowska I, Socha P, Tylki-Szymanska A . Pediatric Liver Disease Patients and Secondary Glycosylation Abnormalities. Front Pediatr. 2021; 8:613224. PMC: 7838542. DOI: 10.3389/fped.2020.613224. View

10.

Lefeber D, Morava E, Jaeken J . How to find and diagnose a CDG due to defective N-glycosylation. J Inherit Metab Dis. 2011; 34(4):849-52. PMC: 3137781. DOI: 10.1007/s10545-011-9370-0. View

11.

Kapusta L, Zucker N, Frenckel G, Medalion B, Ben Gal T, Birk E . From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG). Heart Fail Rev. 2012; 18(2):187-96. PMC: 3593007. DOI: 10.1007/s10741-012-9302-6. View

12.

Pascoal C, Francisco R, Ferro T, Dos Reis Ferreira V, Jaeken J, Videira P . CDG and immune response: From bedside to bench and back. J Inherit Metab Dis. 2019; 43(1):90-124. DOI: 10.1002/jimd.12126. View

13.

Sturiale L, Bianca S, Garozzo D, Terracciano A, Agolini E, Messina A . ALG12-CDG: novel glycophenotype insights endorse the molecular defect. Glycoconj J. 2019; 36(6):461-472. DOI: 10.1007/s10719-019-09890-2. View

14.

Lipinski P, Bogdanska A, Tylki-Szymanska A . Congenital disorders of glycosylation: Prevalence, incidence and mutational spectrum in the Polish population. Mol Genet Metab Rep. 2021; 27:100726. PMC: 7892981. DOI: 10.1016/j.ymgmr.2021.100726. View

15.

Taday R, Gruneberg M, DuChesne I, Reunert J, Marquardt T . Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG). Orphanet J Rare Dis. 2020; 15(1):258. PMC: 7510076. DOI: 10.1186/s13023-020-01528-z. View

16.

Mention K, Lacaille F, Valayannopoulos V, Romano S, Kuster A, Cretz M . Development of liver disease despite mannose treatment in two patients with CDG-Ib. Mol Genet Metab. 2007; 93(1):40-3. DOI: 10.1016/j.ymgme.2007.08.126. View

17.

Koch J, Mayr J, Alhaddad B, Rauscher C, Bierau J, Kovacs-Nagy R . CAD mutations and uridine-responsive epileptic encephalopathy. Brain. 2016; 140(2):279-286. DOI: 10.1093/brain/aww300. View

18.

Barone R, Fiumara A, Jaeken J . Congenital disorders of glycosylation with emphasis on cerebellar involvement. Semin Neurol. 2014; 34(3):357-66. DOI: 10.1055/s-0034-1387197. View

19.

Carmody L, Blau H, Danis D, Zhang X, Gourdine J, Vasilevsky N . Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes. Orphanet J Rare Dis. 2020; 15(1):40. PMC: 7001271. DOI: 10.1186/s13023-020-1313-0. View

20.

Wopereis S, Morava E, Grunewald S, Adamowicz M, Huijben K, Lefeber D . Patients with unsolved congenital disorders of glycosylation type II can be subdivided in six distinct biochemical groups. Glycobiology. 2005; 15(12):1312-9. DOI: 10.1093/glycob/cwj017. View