Abstract
Summary: Congenital disorders of glycosylation (CDGs) are due to defects in the synthesis of the glycan moiety of glycoproteins or other glycoconjugates. This review is devoted mainly to the clinical aspects of protein glycosylation defects. There are two main types of protein glycosylation: N-glycosylation and O-glycosylation. N-glycosylation generally consists of an assembly pathway (in cytosol and endoplasmic reticulum) and a processing pathway (in endoplasmic reticulum and Golgi). O-glycosylation lacks a processing pathway but is otherwise more complex. Sixteen disease-causing defects are known in protein glycosylation: 12 in N-glycosylation and four in O-glycosylation. The N-glycosylation defects comprise eight assembly defects (CDG-I) designated CDG-Ia to CDG-Ih, and four processing defects (CDG-II) designated CDG-IIa to CDG-IId. By far the most frequent is CDG-Ia (phosphomannomutase-2 deficiency). It affects the nervous system and many other organs. Its clinical expression varies from extremely severe to very mild (and thus probably underdiagnosed). The most interesting disease in this group is CDG-Ib (phosphomannose isomerase deficiency) because it is so far the only efficiently treatable CDG (mannose treatment). It hasahepatic–intestinal presentation. The O-glycosylation defects comprise two O-xylosylglycan defects (a progeroid variant of Ehlers–Danlos syndrome and the multiple exostoses syndrome) and two O-mannosylglycan defects (Walker–Warburg syndrome and muscle–eye–brain disease). All known CDGs have a recessive inheritance except for multiple exostoses syndrome, which is dominantly inherited. There is a rapidly growing group of putative CDGs with a large spectrum of clinical presentations (CDG-x). Serum transferrin isoelectrofocusing remains the cornerstone of the screening for N-glycosylation defects associated with sialic acid deficiency. Abnormal patterns can be grouped in to type 1 and type 2. However, a normal pattern does not exclude these defects. Screening for the other CDGs is much more difficult, particularly when the defect is organ- or system-restricted. The latter group promises to become an important new chapter in CDG. It is concluded that CDGs will eventually cover the whole clinical spectrum of paediatric and adult disease manifestations.
Access this article
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Similar content being viewed by others
REFERENCES
Acarregui MJ, George TN, Rhead WJ (1998) Carbohydrate-deficient glycoprotein syndrome type I with profound thrombocytopenia and normal phosphomannomutase and phosphomannose isomerase activities. J Pediatr 133: 697-700.
Aebi M, Hennet T (2001) Congenital disorders of glycosylation: genetic model systems lead the way. Trends Cell Biol 11: 136-141.
Alton G, Hasilik M, Niehues R, et al (1998) Direct utilization of mannose for mammalian glycoprotein biosynthesis. Glycobiology 8: 285-295.
Asano M, Furukawa K, Kido M, et al (1997) Growth retardation and early death of b-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells. EMBO J 16: 1850-1857.
Assmann B, Hackler R, Peters V, et al (2001) A new subtype of a congenital disorder of glycosylation (CDG) with mild clinical manifestations. Neuropediatrics 32: 313-318.
Barone R, Pavone V, Pennisi P, Fiumara A, Fiore CE (2002) Assessment of skeletal status in patients with congenital disorder of glycosylation type Ia. Int J Tissue React 24: 23-28.
Beltrán-Valero de Bernabé D, Currier S, Steinbrecher A, et al (2002) Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome. Am J Hum Genet 71: 1033-1043.
Bhattacharyya R, Bhaumik M, Raju TS, Stanley P (2002) Truncated, inactive N-acetylglucosaminyltransferase III (GlcNAc-TIII) induces neurological and other traits absent in mice that lack Glc-NAc-TIII. J Biol Chem 277: 26300-26309.
Briones P, Vilaseca MA, Garcia-Silva MT, et al (2001) Congenital disorders of glycosylation (CDG) may be underdiagnosed when mimicking mitochondrial disease. Eur J Paediatr Neurol 5: 127-131.
Brockington M, Blake DJ, Prandini P, et al (2001a) Mutations in the Fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin a2 deficiency and abnormal glycosylation of a-dystroglycan. Am J Hum Genet 69: 1198-1209.
Brockington M, Yura Y, Prandini P, et al (2001b) Mutations in the Fukutin related protein gene (FKRP) identifies limb-girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Hum Mol Genet 10: 2851-2859.
Buist N, Grompe M, Steiner R, Miura Y, O'Brien J, Freeze HH (2000) Yet another congenital disorder of glycosylation! (CDGS). J Inherit Metab Dis 23(supplement 1): 187.
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: 647-652.
Burlina AB, Bonafé L, Van Schaftingen E, Jaeken J (2000) Congenital defects of glycosylation with retardation-dysmorphy syndrome and myopathic changes. J Inherit Metab Dis 23(supplement 1): 180.
Chantret I, Dancourt J, Dupré T, et al (2002a) A deficiency in dolichyl-P-glucose: Glc1Man9GlcNAc2-PP-dolichyl a3-glucosyltransferase defines a new subtype of congenital disorders of glycosylation (CDG). J Biol Chem. Dec. 11 [e-pub. ahead of print].
Chantret I, Dupré T, Delenda C, et al (2002b) Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose: Man7GlcNAc2-PP-dolichyl mannosyltransferase. J Biol Chem 277: 25815-25822.
Chui D, Sellakumar G, Green RS, et al (2001) Genetic remodeling of protein glycosylation in vivo induces autoimmune disease. Proc Natl Acad Sci USA 98: 1142-1147.
Clayton P, Winchester B, di Tomaso E, Young E, Keir G, Rodeck C (1993) Carbohydrate-deficient glycoprotein syndrome: normal glycosylation in the fetus. Lancet 341: 956.
Cormand B, Pihko H, Bayes M, et al (2001) Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye-brain disease. Neurology 56: 1059-1069.
Cormier-Daire V, Amiel J, Vuillaumier-Barrot S, et al (2000) Congenital disorders of glycosylation IIa cause growth retardation, mental retardation, and facial dysmorphism. J Med Genet 37: 875 876.
de Koning TJ, Dorland J, van Diggelen OP, et al (1998) A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency. Biochem Biophys Res Commun 245: 38-42.
de Lonlay P, Cuer M, Vuillaumier-Barrot S, et al (1999) Hyperinsulinemic hypoglycemia as a presenting sign in phosphomannose isomerase deficiency: a new manifestation of carbohydrate deficient glycoprotein syndrome treatablewithmannose. J Pediatr 135: 379-383.
de Lonlay P, Seta N, Barrot S, et al (2001) A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases. J Med Genet 38: 14-19.
De Praeter CM, Gerwig GJ, Bause E, et al (2000) A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency. Am J Hum Genet 66: 1744-1756.
Demetriou M, Granovsky M, Quaggin S, Dennis JW (2001) Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409:733-739.
Dorland L, de Koning TJ, Toet M, de Vries LS, van den Berg IET, Poll-Thé BT (1997) Recurrent non-immune hydrops fetalis associated with carbohydrate-deficient glycoprotein syndrome. J Inherit Metab Dis 20(supplement 1): 88.
Durand G, Seta N (2000) Protein glycosylation and diseases: blood and urinary oligosaccharides as markers for diagnosis and therapeutic monitoring. Clin Chem 46: 795-805.
Eisenberg I, Avidan N, Potikha T, et al (2001) The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nature Genet 29: 83-87.
Enns GM, Steiner RD, Buist N, et al (2002) Clinical and molecular features of congenital disorder of glycosylation in patients with type 1 sialotransferrin pattern and diverse ethnic origin. J Pediatr 141: 695-700.
Etzioni A, Frydman M, Pollack S, et al (1992) Recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med 327: 1789-1792.
Eyskens F, Ceuterick C, Martin JJ, Jansens G, Jaeken J (1994) Carbohydrate-deficient glycoprotein syndrome with previously unreported features. Acta Paediatr 83: 892-896.
Fiumara A, Sorge G, Meli C, Barone R, Pavone L (2002) IEF type 1 in COFS/Pena-Shokeir syndrome. A new form of CDG(Ix) with evidence of metabolic defect causing multiple malformations. J Inherit Metab Dis 25 (supplement 1): 134.
Fletcher JM, Matthijs G, Jaeken J, Van Schaftingen E, Nelsen PV (2000) Carbohydrate-deficient glycoprotein syndrome: beyond the screen. J Inherit Metab Dis 23: 396-398.
Freeze HH (2001) Update and perspectives on congenital disorders of glycosylation. Glycobiology 11: 129R-143R.
Freeze HH (2002) Human disorders in N-glycosylation and animal models. Biochim Biophys Acta 1573: 388-393.
Garcia Silva MT, Briones P, Schollen E, et al (2002) Congenital disorder of glycosylation (CDG) type IE. A new patient. J Inherit Metab Dis 25 (supplement 1): 133.
Grubenmann CE, Frank CG, Kjaergaard S, Berger EG, Aebi M, Hennet T (2002) ALG12 mannosyltransferase defect in congenital disorder of glycosylation type Ig. Hum Mol Genet 11: 2331-2339.
Grünewald S, Imbach T, Huijben K, et al (2000) Clinical and biochemical characteristics of congenital disorder of glycosylation type Ic, the first recognized endoplasmic reticulum defect in N-glycan synthesis. Ann Neurol 47: 776-781.
Grünewald S, Schollen E, Van Schaftingen E, Jaeken J, Matthijs G (2001) High residual acitivity of PMM2 in patients' fibroblasts: possible pitfall in the diagnosis of CDG-Ia phosphomannomutase deficiency). Am J Hum Genet 68: 347-354.
Grünewald S, Matthijs G, Jaeken J (2002) Congenital disorders of glycosylation: a review. Pediatr Res 52: 618-624.
Hansske B, Thiel C, Lübke T, et al (2002) Deficiency of UDP-galactose:N-acetylglucosamine b-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId. J Clin Invest 109: 725-733.
Harms HK, Zimmer KP, Kurnik K, Bertele-Harms RM, Weidinger S, Reiter K (2002) Oral mannose therapy persistently corrects the severe clinical symptoms and biochemical abnormalities of phosphomannose isomerase deficiency. Acta Paediatr 91: 1065-1072.
Hayashi YK, Ogawa M, Tagawa K, et al (2001) Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy. Neurology 57: 115-121.
Helenius J, Aebi M (2002) Transmembrane movement of dolichol linked carbohydrates during N-glycoprotein biosynthesis in the endoplasmic reticulum. Semin Cell Dev Biol 13: 171-178.
Hendriksz CJ, McClean P, Henderson MJ, et al (2001) Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with oral mannose. Arch Dis Child 85: 339-340.
Hennet T (2002) The galactosyltransferase family. Cell Mol Life Sci 59: 1081-1095.
Hinderlich S, Eisenberg I, Horstkorte R, Reutter W, Mitrani-Rosenbaum S (2002) Is hereditary inclusion body myopathy a glycosylation disease? Glycobiology 12: 643.
Hirschberg CB, Robbins PW, Abeijon C (1998) Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus. Annu Rev Biochem 67: 49-69.
Huemer M, Huber W-D, Schima W, et al (2000) Budd-Chiari syndrome associated with coagulation abnormalities in a child with carbohydrate deficient glycoprotein syndrome type Ix. J Pediatr 136: 691-695.
Imbach T, Schenk B, Schollen E, et al (2000) Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of glycosylation type Ie. J Clin Invest 105: 233-239.
Jaeken J, Carchon H(2001) Congenital disorders of glycosylation: the rapidly growing tip of the iceberg. Curr Opin Neurol 14: 811-815.
Jaeken J, Matthijs G (2001) Congenital disorders of glycosylation. Annu Rev Genomics Hum Genet 2: 129-151.
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: 179.
Jaeken J, van Eijk HG, van der Heul C, Corbeel L, Eeckels R, Eggermont E (1984) Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome. Clin Chim Acta 144: 245-247.
Jaeken J, Schachter H, Carchon H, De Cock P, Coddeville B, Spik G (1994) Carbohydrate-deficient glycoprotein syndrome type II: a deficiency in Golgi localised N-acetyl-glucosaminyltransferase II. Arch Dis Child 71: 123-127.
Jaeken J, Matthijs G, Saudubray JM, et al (1998) Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation. Am J Hum Genet 62: 1535-1539.
Jaeken J, Imbach T, Schenk B, et al (2000) A newly recognized glycosylation defect with psychomotor retardation, ichthyosis and dwarfism. J Inherit Metab Dis 23(supplement 1): 186.
Jaeken J, Matthijs G, Carchon H, Van Schaftingen E (2001) Defects of N-glycan synthesis. In Scriver CR, Beaudet WS, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 1601-1621.
Kano H, Kobayashi K, Herrmann R, et al (2002) Deficiency of a-dystroglycan in muscle-eye-brain disease. Biochem Biophys Res Commun 291: 1283-1286.
Kim S, Westphal V, Srikrishna G, et al (2000) Dolichol phosphate mannose synthase (DPM1) mutations define congenital disorder of glycosylation Ie (CDG-Ie). J Clin Invest 105: 191-198.
Kjaergaard S, Schwartz M, Skovby F (2001) Congenital disorder of glycosylation type Ia (CDG-Ia): phenotypic spectrum of the R141H/F119L genotype. Arch Dis Child 85: 236-239.
Kjaergaard S, Müller J, Skovby F (2002) Prepubertal growth in congenital disorder of glycosylation type Ia (CDG-Ia). Arch Dis Child 87: 324-327.
Kobata A (1992) Structures and functions of the sugar chains of glycoproteins. Eur J Biochem 209: 483-501.
Körner C, Knauer R, Stephani U, Marquardt T, Lehle L, von Figura K (1999) Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man: Man5GlcNAc2-PP-dolichyl mannosyltransferase. EMBO J 18: 6816-6822.
Kornfeld R, Kornfeld S (1985) Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 54: 631-664.
Kranz C, Denecke J, Lehrman MA, et al (2001a) A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If). J Clin Invest 108: 1613-1619.
Kranz C, Sagi D, Denecke J, et al (2001b) Defective galactosylation in congenital disorder of glycosylation type x (CDG-x). J Inherit Metab Dis 24 (supplement 1): 113.
Lammens M (2000) Neuronal migration disorders in man. Eur J Morphol 38: 327-333.
Leonard J, Grünewald S, Clayton P (2001) Diversity of congenital disorders of glycosylation. Lancet 357: 1382-1383.
Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Körner C (2001) Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nature Genetics 28: 73-76.
Lühn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D (2001) The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nature Genetics 28: 69-72.
Marquardt T, Freeze HH (2001) Congenital disorders of glycosylation: glycosylation defects in man and biological models for their study. Biol Chem 382: 161-177.
Marquardt T, Hasilik M, Niehues R, et al (1997) Mannose therapy in carbohydrate-deficient glycoprotein syndrome type 1: first results of the German multicenter study. Amino Acids 12: 389.
Matthijs G, Schollen E, Pardon E, et al (1997) Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). Nature Genetics 16: 88-92.
Mention K, Michaud L, Dobbelaere D, Guimber D, Gottrand F, Turck D (2001) Neonatal severe intractable diarrhoea as the presenting manifestation of an unclassified congenital disorder of glycosylation (CDG-x). Arch Dis Child Fetal Neonatal Ed 85: F217-F219.
Michele DE, Barresi R, Kanagawa M, et al (2002) Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies. Nature 418: 417-422.
Mills P, Mills K, Clayton P, Johnson A, Whitehouse D, Winchester B (2001) Congenital disorders of glycosylation type I leads to altered processing of N-linked glycans, as well as underglycosylation. Biochem J 359: 249-254.
Moore SA, Saito F, Chen J, et al (2002) Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 418: 422-425.
Muntoni F, Brockington M, Blake DJ, Torelli S, Brown SC (2002) Defective glycosylation in muscular dystrophy. Lancet 360: 1419-1421.
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: 1414-1420.
Okajima T, Fukumoto S, Furukawa K, Urano T, Furukawa K (1999) Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. J Biol Chem 274: 28841-28844.
Panneerselvam K, Freeze HH (1996) Mannose corrects altered N-glycosylation in carbohydrate-deficient glycoprotein syndrome fibroblasts. J Clin Invest 97: 1478-1487.
Parodi AJ (2000) Protein glucosylation and its role in protein folding. Annu Rev Biochem 69: 69-93.
Peters V, Penzien JM, Reiter G, et al (2002) Congenital disorder of glycosylation IId (CDG-IId)-A new entity: clinical presentation with Dandy-Walker malformation and myopathy. Neuropediatrics 33: 27-32.
Prietsch V, Peters V, Hackler R, et al (2002) A new case of CDG-x with stereotyped dystonic hand movements and optic atrophy. J Inherit Metab Dis 25: 126-130.
Quelhas D, Vilarinho L, Teles EL, et al (2001) Congenital disorders of glycosylation type-x with type 2 pattern of transferrin isolectric focusing. J Inherit Metab Dis 24 (supplement 1): 112.
Quentin E, Gladen A, Roden L, Kresse H (1990) A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. Proc Natl Acad Sci USA 87: 1342-1346.
Ramaekers VT, Stibler H, Kint J, Jaeken J (1991) A new variant of the carbohydrate deficient glycoprotein syndrome. J Inherit Metab Dis 14: 385-388.
Ross ME (2002) Full circle to cobbled brain. Nature 418: 376-377.
Rudd PM, Elliott T, Creswell P, Wilson IA, Dwek RA (2001) Glycosylation and the immune system. Science 291: 2370-2376.
Sala G, Dupré T, Seta N, Codogno P, Ghidoni R (2002) Increased biosynthesis of glycosphingolipids in congenital disorder of glycosylation Ia (CDG-Ia) fibroblasts. Pediatr Res 52: 645-651.
Schachter H (1991) The 'yellow brick road' to branched complex N-glycans. Glycobiology 1: 453-461.
Schachter H (2001) Congenital disorders involving defective N-glycosylation of proteins. Cell Mol Life Sci 58: 1085-1104.
Schenk B, Imbach T, Frank CG, et al (2001) MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If. J Clin Invest 108: 1687-1695.
Smith PL, Myers JT, Rogers CE, et al (2002) Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus. J Cell Biol 158: 801-815.
Stanley P, Ioffe E (1995) Glycosyltransferase mutants: key to new insights in glycobiology. FASEB J 9: 1436-1444.
Stibler H, Stephani U, Kutsch U (1995) Carbohydrate-deficient glycoprotein syndrome: a fourth subtype. Neuropediatrics 26: 235-237.
Stibler H, Gylje H, Uller A (1999) A neurodystrophic syndrome resembling carbohydrate-deficient glycoprotein syndrome type III. Neuropediatrics 30: 90-92.
Sturla P, Puglielli L, Tonetti M, et al (2001) Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LADII patients. Pediatr Res 49: 537-542.
Sturla L, Rampal R, Haltiwanger RS, Zanardi D, Etzioni A, Tonetti M(2002) Characterization of the residual fucose-containing glycoconjugates in LADII/CDGS IIc cells. Glycobiology 12: 664.
Subhedar NV, Isherwood DM, Davidson DC (1996) Hyperglycinaemia in a child with carbohydrate-deficient glycoprotein syndrome type I. J Inherit Metab Dis 19: 796-797.
Thiel C, Schwarz M, Hasilik M, et al (2002) Deficiency of dolichyl-P-Man: Man7GlcNAc2-PP-dolichyl mannosyltransferase causes congenital disorder of glycosylation type Ig. Biochem J 367: 195-201
Van den Steen P, Rudd PM, Dwek RA, Opdenakker G (1998) Concepts and principles of O-linked glycosylation. Crit Rev Biochem Mol Biol 33: 151 208.
Van Dijk W, Koeleman C, Van het Hof B, Poland D, Jakobs C, Jaeken J (2001) Increased a3-fucosylation of a1-acid glycoprotein in patients with congenital disorder of glycosylation type IA (CDG-Ia). FEBS Lett 494: 232-235.
van Eijk HG, Van Noort WL, Dubelaar M-L, Van der Heul C (1983) The microheterogeneity of human transferrins in biological fluids. Clin Chim Acta 132: 167-171.
Van Geet C, Jaeken J, Freson K, et al (2001) Congenital disorders of glycosylation Ia and IIa are associated with different primary haemostatic complications. J Inherit Metab Dis 24: 477-492.
Van Maldergem L, Jaeken J (2001) Two siblings with severe mental retardation, facial dysmorphia and ectopic kidneys and a type 2 pattern of serum sialotransferrin isoelectrofocusing. J Inherit Metab Dis 24: (supplement 1): 112.
Van Schaftingen E, Jaeken J (1995) Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett 377: 318-320.
Varki A (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3: 97-130.
Varki A, Marth J (1995) Oligosaccharides in vertebrate development. Dev Biol 6: 127-138.
Völker C, De Praeter CM, Hardt B, et al (2002) Processing of N-linked carbohydrate chains in a patient with glucosidase I deficiency (CDG type IIb). Glycobiology 12: 473-483.
Wada Y, Nishikawa A, Okamoto N, et al (1992) Structure of serum transferrin in carbohydrate-deficient glycoprotein syndrome. BiochemBiophys Res Commun 189: 832-836.
Wang Y, Tan J, Sutton-Smith M, et al (2001) Modeling human congenital disorder of glycosylation type IIa in the mouse: conservation of asparagine-linked glycan-dependent functions in mammalian physiology and insights into disease pathogenesis. Glycobiology 11: 1051-1070.
Westphal V, Kjaergaard S, Davis JA, Peterson SM, Skovby F, Freeze HH (2001) Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation. Mol Genet Metab 73: 77-85.
Wicklund CL, Pauli RM, Johnston D, Hecht JT (1995) Natural history study of hereditary multiple exostoses. Am J Med Genet 55: 43-46.
Willer T, Amselgruber W, Deutzmann R, Strahl S (2002) Characterization of POMT2, a novel member of the PMT protein O-mannosyltransferase family specifically localized to the acrosome of mammalian spermatids. Glycobiology 12: 771-783.
Wuyts W, Van Hul W(2000) Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes. Hum Mutat 15: 220-227.
Yamashita K, Ohkura T, Ideo H, Ohno K, Kanai M (1993) Electrospray ionization mass spectrometric analysis of serum transferrin isoforms in patients with carbohydrate-deficient glycoprotein syndrome. J Biochem 114: 766-769.
Yoshida A, Kobayashi K, Manya H, et al (2001) Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Dev Cell 1: 717-724.
Zak BM, Crawford BE, Esko JD (2002) Hereditary multiple exostoses and heparan sulfate polymerisation. Biochim Biophys Acta 1573: 346-355.
Zdebska E, Golaszewska E, Fabijanska-Mitek J, et al (2001a) Glycoconjugate abnormalities in patients with congenital dyserythropoietic anemia type I, II and III. Br J Haematol 114: 907-913.
Zdebska E, Musielak M, Jaeken J, Kościelak J (2001b) Band 3 glycoprotein and glycophorin A from erythrocytes of children with congenital disorder of glycosylation type-Ia are underglycosylated. Proteomics 1: 269-274.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jaeken, J. Congenital disorders of glycosylation (CDG): It's all in it!. J Inherit Metab Dis 26, 99–118 (2003). https://doi.org/10.1023/A:1024431131208
Issue Date:
DOI: https://doi.org/10.1023/A:1024431131208