Congenital Defects of Glycosylation: Disorders of N-Glycan Synthesis

  • Jaak Jaeken


Five inborn errors in the pathway of N-glycan synthesis [also called congenital defects of glycosyla?tion, CDG syndromes] are known and are depicted in Fig. 38.1. Phosphomannomutase (PMM) deficiency, reported in the large majority of these patients, is a multisystem disease with, as a rule, severe brain involvement.


Serum Transferrin Leukocyte Adhesion Deficiency Guanosine Diphosphate Congenital Dyserythropoietic Anemia Leukocyte Adhesion Deficiency Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jaeken J, Vanderschueren-Lodeweyckx M, Casaer P et al. (1980) Familial psychomotor retardation with markedly fluctuating serum proteins, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome? Pediatr Res 14: 179CrossRefGoogle Scholar
  2. 2.
    Jaeken J, Carchon H, Stibler H (1993) The carbohydrate-deficient glycoprotein syndromes: pre-Golgi and Golgi disorders? Glycobiology 3:423–428Google Scholar
  3. 3.
    Jaeken J, Stibler H, Hagberg B (1991) The carbohydrate-deficient glycoprotein syndrome: a new inherited multisystemic disease with severe nervous system involvement. Acta Paediatr Scand [Supplì 375: 1–71Google Scholar
  4. 4.
    Jaeken J, Matthijs G, Barone R, Carchon H (1997) Carbohydrate deficient glycoprotein ( CDG) syndrome type I. J Med Genet 34: 73–76Google Scholar
  5. 5.
    Van Schaftingen E, Jaeken J (1995) Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett 377: 318–320Google Scholar
  6. 6.
    Jaeken J, Besley G, Buist N et al. (1996) Phosphomannomutase deficiency is the major cause of carbohydrate-deficient glycoprotein syndrome type I. J Inherit Metab Dis 19 [Supp11]: 6Google Scholar
  7. 7.
    de Zegher F, Jaeken J (1995) Endocrinology of the carbohydrate-deficient glycoprotein syndrome type from birth through adolescence. Pediatr Res 37:395–401Google Scholar
  8. 8.
    Van Geet C, Jaeken J (1993) A unique pattern of coagulation abnormalities in carbohydrate-deficient glycoprotein syndrome. Pediatr Res 33:540-541Google Scholar
  9. 9.
    Jaeken J, van Eijk HG, van der Heul C et al. (1984) Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome. Clin Chim Acta 144:245–247Google Scholar
  10. 10.
    Panneerselvam K, Freeze HH (1996) Mannose corrects altered N-glycosylation in carbohydrate-deficient glycoprotein syndrome fibroblasts. J Clin Invest 97: 1478–1487PubMedCrossRefGoogle Scholar
  11. 11.
    Kjaergaard S, Kristiansson B, Stibler H et al. (1998) Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type I A. Acta Paediatr 87: 884–888PubMedCrossRefGoogle Scholar
  12. 12.
    Matthijs G, Schollen E, Van Schaftingen E, Cassiman J-J, Jaeken J (1998) Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1 A. Am J Hum Genet 62:542–550Google Scholar
  13. 13.
    Niehues R, Hasilik M, Alton G et al. (1998) Carbohydrate-deficient glycoprotein syndrome type Ib: phosphomannose isomerase deficiency and mannose therapy. J Clin Invest 101: 1414–1420PubMedCrossRefGoogle Scholar
  14. 14.
    de Koning TJ, Dorland L, van Diggelen OP et al. (1998) A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency. Biochem Biophys Res Commun 245: 38–42PubMedCrossRefGoogle Scholar
  15. 15.
    Jaeken J, Matthijs G, Saudubray J-M et al. (1985) Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation. Am J Hum Genet 62:1535–1539Google Scholar
  16. 16.
    Pelletier VA, Galeano N, Brochu P et al. (1985) Secretory diarrhea with protein-losing enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia and congenital hepatic fibrosis: a new syndrome. J Pediatr 108: 61–65Google Scholar
  17. 17.
    Sturla L, Etzioni A, Bisso A et al. (1998) Defective intracellular activity of GDP-D-mannose-4, 6-dehydratase in leukocyte adhesion deficiency type II syndrome. FEBS Lett 429: 274–278Google Scholar
  18. 18.
    Burda P, Borsig L, de Rijk-van Andel J et al. (1998) A novel carbohydrate-deficient glycoprotein syndrome characterized by a deficiency in glucosylation of the dolichol-linked oligosaccharide. J Clin Invest 102: 647–652PubMedCrossRefGoogle Scholar
  19. 19.
    Körner C, Knauer R, Holzbach U et al. (1998) Carbohydrate-deficient glycoprotein syndrome type V: deficiency of dolichyl-P-Glc:Man9 GlcNAc,,-PP-dolichyl glucosyltransfer-ase. Proc Natl Acad Sci USA 95: 13200–13205PubMedCrossRefGoogle Scholar
  20. 20.
    Ramaekers VT, Stibler H, Kint J, Jaeken J (1991) A new variant of the carbohydrate deficient glycoproteins syndrome. J Inherit Metab Dis 14:385–388Google Scholar
  21. 21.
    Jaeken J, Schachter H, Carchon H et al. (1994) Carbohydrate-deficient glycoprotein syndrome type II: a deficiency in Golgi localised N-acetyl-glucosaminyltransferase II. Arch Dis Child 71: 123–127Google Scholar
  22. 22.
    Tan J, Dunn J, Jaeken J, Schachter H (1996) Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development. Am J Hum Genet 59: 810–817PubMedGoogle Scholar
  23. 23.
    Stibler H, Westerberg B, Hanefeld F, Hagberg B (1993) Carbohydrate-deficient glycoprotein (CDG) syndrome–a new variant, type III. Neuropediatrics 24: 51–52Google Scholar
  24. 24.
    Eyskens F, Ceuterick C, Martin J-J, Janssens G, Jaeken J (1994) Carbohydrate-deficient glycoprotein syndrome with previously unreported features. Acta Paediatr 83: 892–896PubMedCrossRefGoogle Scholar
  25. 25.
    Stibler H, Stephani U, Kutsch U (1995) Carbohydrate-deficient glycoprotein syndrome - a fourth subtype. Neuro-pediatrics 26:235-237Google Scholar
  26. 26.
    Skladal D, Sperl W, Henry H, Bachmann C (1996) Congenital cataract and familial brachydactyly in carbohydrate-deficient glycoprotein syndrome. J Inherit Metab Dis 19: 251–252PubMedCrossRefGoogle Scholar
  27. 27.
    Assmann B, Hoffmann GF, Köhler M et al. (1997) CDGsyndrome type I with normal phosphomannomutase activity and unusually mild clinical manifestations. Amino Acids 12: 387CrossRefGoogle Scholar
  28. 28.
    Dorland L, de Koning TJ, Toet M et al. (1997) Recurrent non-immune hydrops fetalis associated with carbohydrate-deficient glycoprotein syndrome. J Inherit Metab Dis 20 [Suppl 1]: 88Google Scholar
  29. 29.
    Gasparini P, Miraglia del Giudice E, Delaunay J et al. (1997) Localization of the congenital dyserythropoietic anemia II locus to chromosome 2ogn.2 by genomewide search. Am J Hum Genet 61: 1112–1116PubMedCrossRefGoogle Scholar
  30. 30.
    Körner C, Knauer R, Stephani U et al. (1999) Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man5GIcNAc,-PP-dolichylmannosyltransferase. EMBO J 18: 6816–6822Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Jaak Jaeken

There are no affiliations available

Personalised recommendations