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Immunological aspects of congenital disorders of glycosylation (CDG): a review

  • Review
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Congenital disorders of glycosylation (CDG) are a rapidly growing family of genetic diseases comprising more than 85 known distinct disorders. They show a great phenotypic variability ranging from multi-organ/system to mono-organ/system involvement with very mild to extremely severe expression. Immunological dysfunction has a significant impact on the phenotype in a minority of CDG. CDG with major immunological involvement are ALG12-CDG, MAGT1-CDG, MOGS-CDG, SLC35C1-CDG and PGM3-CDG. This review discusses the variety of immunological abnormalities reported in human CDG. Understanding the immunological aspects of CDG may contribute to a better management/treatment of these pathologies and possibly of more common diseases, such as inflammatory diseases.

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Abbreviations

Asn:

Asparagine

CDG:

Congenital disorder(s) of glycosylation

CD:

Cluster of differentiation

EBV:

Epstein-Barr virus

ER:

Endoplasmic reticulum

GalNAc:

N-acetylgalactosamine

GDP:

Guanosine diphosphate

GlcNAc:

N-acetylglucosamine

Glu:

Glucose

GPI:

Glycosylphosphatidylinositol

HSCT:

Hematopoietic stem cell transplantation

IEF:

Isoelectric focusing

IFN-γ:

Interferon-gamma

IL-:

Interleukin

Man:

Mannose

NK:

Natural killer

NKG2D:

Natural killer activating receptor group 2, member D

sLex:

Sialyl-Lewis X

OST:

Oligosaccharyltransferase

TCR:

T cell receptor

Thr:

Threonine

TLR:

Toll like receptor

UDP:

Uridine diphosphate

XMEN:

X-linked immunodeficiency with magnesium defect and EBV infection and neoplasia

References

  • Al-Essa M, Dhaunsi GS, Al-Qabandi W, Khan I (2013) Impaired NADPH oxidase activity in peripheral blood lymphocytes of galactosemia patients. Exp Biol Med 238:779–786

    Article  CAS  Google Scholar 

  • Anthony RM, Ravetch JV (2010) A novel role for the IgG Fc glycan: the anti-inflammatory activity of sialylated IgG Fcs. J Clin Immunol 30(Suppl 1):S9–14

    Article  CAS  PubMed  Google Scholar 

  • Apweiler R, Hermjakob H, Sharon N (1999) On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochim Biophys Acta 1473:4–8

    Article  CAS  PubMed  Google Scholar 

  • Arnoux JB, Boddaert N, Valayannopoulos V et al (2008) Risk assessment of acute vascular events in congenital disorder of glycosylation type Ia. Mol Genet Metab 93:444–449

  • Barral DC, Brenner MB (2007) CD1 antigen presentation: how it works. Nat Rev Immunol 7:929–941

    Article  CAS  PubMed  Google Scholar 

  • Baum LG, Crocker PR (2009) Glycoimmunology: ignore at your peril! Immunol Rev 230:5–8

    Article  CAS  PubMed  Google Scholar 

  • Bergmann M, Gross HJ, Abdelatty F, Möller P, Jaeken J, Schwartz-Albiez R (1998) Abnormal surface expression of sialoglycans on B lymphocyte cell lines from patients with carbohydrate deficient glycoprotein syndrome I A (CDGS I A). Glycobiology 8:963–972

    Article  CAS  PubMed  Google Scholar 

  • Berry GT (1993) Classic galactosemia and clinical variant galactosemia. In Pagon RA, Adam MP, Ardinger HH et al (Eds.) GeneReviews, Seattle

  • Berry G (2000) Classic galactosemia and clinical variant galactosemia. GeneReviews, Seattle

  • Björklund JE, Stibler H, Kristiansson B, Johansson SG, Magnusson CG (1997) Immunoglobulin levels in patients with carbohydrate-deficient glycoprotein syndrome type I. Int Arch Allergy Immunol 114:116–119

    Article  PubMed  Google Scholar 

  • Blank C, Smith LA, Hammer DA (2006) Recurrent infections and immunological dysfunction in congenital disorder of glycosylation Ia (CDG Ia). J Inherit Metab Dis 29:592

    Article  CAS  PubMed  Google Scholar 

  • Bosch AM (2006) Classical galactosaemia revisited. J Inherit Metab Dis 29:516–525

    Article  CAS  PubMed  Google Scholar 

  • Buerki SE, Grandgirard D, Datta AN et al (2016) Inflammatory markers in pediatric stroke: an attempt to better understanding the pathophysiology. Eur J Paediatr Neurol 20:252–60

    Article  PubMed  Google Scholar 

  • Butler M, Quelhas D, Critchley AJ et al (2003) Detailed glycan analysis of serum glycoproteins of patients with congenital disorders of glycosylation indicates the specific defective glycan processing step and provides an insight into pathogenesis. Glycobiology 13:601–622

    Article  CAS  PubMed  Google Scholar 

  • Carlow DA, Gossens K, Naus S, Veerman KM, Seo W, Ziltener HJ (2009) PSGL-1 function in immunity and steady state homeostasis. Immunol Rev 230:75–96

    Article  CAS  PubMed  Google Scholar 

  • Chang J, Block TM, Guo JT (2015) Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections. Antivir Ther 20:257–259

    Article  PubMed  Google Scholar 

  • Chantret I, Dupré T, Delenda C et al (2002) 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

    Article  CAS  PubMed  Google Scholar 

  • Coman D, Irving M, Kannu P, Jaeken J, Savarirayan R (2008) The skeletal manifestations of the congenital disorders of glycosylation. Clin Genet 73:507–515

    Article  CAS  PubMed  Google Scholar 

  • Coss KP, Hawkes CP, Adamczyk B et al (2014) N-glycan abnormalities in children with galactosemia. J Proteome Res 13:385–94

    Article  CAS  PubMed  Google Scholar 

  • Crespo HJ, Lau JT, Videira PA (2013) Dendritic cells: a spot on sialic acid. Front Immunol 4:491

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dauber A, Ercan A, Lee J et al (2014) Congenital disorder of fucosylation type 2c (LADII) presenting with short stature and developmental delay with minimal adhesion defect. Hum Mol Genet 23:2880–2887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Cock P, Jaeken J (2009) MGAT2 deficiency (CDG-IIa): the life of J. Biochim Biophys Acta 1792:844–846

    Article  PubMed  CAS  Google Scholar 

  • De Graaf TW, Van der Stelt ME, Anbergen MG, van Dijk W (1993) Inflammation-induced expression of sialyl Lewis X-containing glycan structures on alpha 1-acid glycoprotein (orosomucoid) in human sera. J Exp Med 177:657–666

    Article  PubMed  Google Scholar 

  • de la Morena-Barrio ME, Hernández-Caselles T, Corral J et al (2013) GPI-anchor and GPI-anchored protein expression in PMM2-CDG patients. Orphanet J Rare Dis 8:170

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Demellawy DE, Chang N, de Nanassy J, Nasr A (2015) GALNT3 gene mutation-associated chronic recurrent multifocal osteomyelitis and familial hyperphosphatemic familial tumoral calcinosis. Scand J Rheumatol 44:170–172

    Article  PubMed  Google Scholar 

  • Dhalla F, Murray S, Sadler R et al (2015) Identification of a novel mutation in MAGT1 and progressive multifocal leucoencephalopathy in a 58-year-old man with XMEN disease. J Clin Immunol 35:112–118

  • Di Rocco M, Hennet T, Grubenmann CE et al (2005) Congenital disorder of glycosylation (CDG) Ig: report on a patient and review of the literature. J Inherit Metab Dis 28:1162–1164

    Article  PubMed  Google Scholar 

  • Dupré T, Barnier A, de Lonlay P et al (2000) Defect in N-glycosylation of proteins is tissue-dependent in congenital disorders of glycosylation Ia. Glycobiology 10:1277–1281

    Article  PubMed  Google Scholar 

  • Eklund EA, Newell JW, Sun L et al (2005) Molecular and clinical description of the first US patients with congenital disorder of glycosylation Ig. Mol Genet Metab 84:25–31

    Article  CAS  PubMed  Google Scholar 

  • Etzioni A, Tonetti M (2000) Fucose supplementation in leukocyte adhesion deficiency type II. Blood 95:3641–3643

    CAS  PubMed  Google Scholar 

  • Etzioni A, Frydman M, Pollack S et al (1992) Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med 327:1789–1792

    Article  CAS  PubMed  Google Scholar 

  • Freeze H, Schachter H et al (2009) Genetic disorders of glycosylation. In: Varki A, Cummings R, Esko J (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  • Frydman M, Etzioni A, Eidlitz-Markus T et al (1992) Rambam-Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and Bombay phenotype. Am J Med Genet 44:297–302

    Article  CAS  PubMed  Google Scholar 

  • Goreta SS, Dabelic S, Dumic J (2012) Insights into complexity of congenital disorders of glycosylation. Biochem Med 22:156–170

    Article  CAS  Google Scholar 

  • Grubenmann CE, Frank CG, Kjaergaard S, Berger EG, Aebi M, Hennet T (2002) ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg. Hum Mol Genet 11:2331–2339

    Article  CAS  PubMed  Google Scholar 

  • Grubenmann CE, Frank CG, Hülsmeier AJ et al (2004) Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik. Hum Mol Genet 13:535–542

    Article  CAS  PubMed  Google Scholar 

  • Grunewald S (2009) The clinical spectrum of phosphomannomutase 2 deficiency (CDG-Ia). Biochim Biophys Acta 1792:827–834

    Article  PubMed  CAS  Google Scholar 

  • Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R (2009) Severe sepsis in cirrhosis. Hepatology 50:2022–33

    Article  CAS  PubMed  Google Scholar 

  • Hayes JM, Cosgrave EF, Struwe WB et al (2014) Glycosylation and Fc receptors. Curr Top Microbiol Immunol 382:165–99

    CAS  PubMed  Google Scholar 

  • He P, Srikrishna G, Freeze HH (2014) N-glycosylation deficiency reduces ICAM-1 induction and impairs inflammatory response. Glycobiology 24:392–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helmus Y, Denecke J, Yakubenia S et al (2006) Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter. Blood 107:3959–3966

  • Heyne K, Mayatepek E, Walther F, Weidinger S, Pahl HL (1998) Pericardial effusion in glycanosis CDG type I (MIM 212 065): an inflammatory endoplasmic reticulum overload response? Eur J Pediatr 157:168–169

    CAS  PubMed  Google Scholar 

  • Hidalgo A, Ma S, Peired AJ, Weiss LA, Cunningham-Rundles C, Frenette PS (2003) Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene. Blood 101:1705–1712

    Article  CAS  PubMed  Google Scholar 

  • Huybrechts S, De Laet C, Bontems P et al (2012) Deficiency of subunit 6 of the conserved oligomeric golgi complex (COG6-CDG): second patient, different phenotype. JIMD Rep 4:103–108

    Article  CAS  PubMed  Google Scholar 

  • Ilkovski B, Pagnamenta AT, O’Grady GL et al (2015) Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies. Hum Mol Genet 24:6146–6159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imtiaz F, Worthington V, Champion M et al (2000) Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type I. J Inherit Metab Dis 23:162–174

    Article  CAS  PubMed  Google Scholar 

  • Jaeken J (2012) MGAT2-CDG (CDG-IIa) and dysmorphism. Am J Med Genet 158A:2974–2975

    Article  PubMed  Google Scholar 

  • Jaeken J, Vanderschueren-Lodeweyckx M, Casaer P, Snoeck L, Corbeel L, Eggermont E, Eeckels R (1980) Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome? Pediatr Res 14:179

    Article  Google Scholar 

  • Jaeken J, De Cock P, Stibler H et al (1993) Carbohydrate-deficient glycoprotein syndrome type II. J Inherit Metab Dis 16:1041

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaeken J, Matthijs G, Barone R, Carchon H (1997) Carbohydrate deficient glycoprotein (CDG) syndrome type I. J Med Genet 34:73–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaeken J, Hennet T, Matthijs G, Freeze HH (2009) CDG nomenclature: time for a change! Biochim Biophys Acta 1792:825–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jamieson JC, McCaffrey G, Harder PG (1993) Sialyltransferase: a novel acute-phase reactant. Comp Biochem Physiol B 105:29–33

    Article  CAS  PubMed  Google Scholar 

  • Jensen T, Galli-Stampino L, Mouritsen S et al (1996) T cell recognition of Tn-glycosylated peptide antigens. Eur J Immunol 26:1342–9

    Article  CAS  PubMed  Google Scholar 

  • Kapusta L, Zucker N, Frenckel G et al (2013) From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG). Heart Fail Rev 18:187–196

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi RH, Kettelhut BV, Kobayashi AL (1983) Galactose inhibition of neonatal neutrophil function. Pediatr Infect Dis 2:442–445

    Article  CAS  PubMed  Google Scholar 

  • Kranz C, Denecke J, Lehle L et al (2004) Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase I. Am J Hum Genet 74:545–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kranz C, Basinger AA, Güçsavaş-Calikoğlu M et al (2007a) Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality. Am J Med Genet A 143A:1371–1378

    Article  CAS  PubMed  Google Scholar 

  • Kranz C, Jungeblut C, Denecke J et al (2007b) A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy. Am J Hum Genet 80:433–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kundak AA, Zenciroğlu A, Yaralı N et al (2012) An unusual presentation of galactosemia: hemophagocytic lymphohistiocytosis. Turk J Haematol 29:401–404

    Article  PubMed  PubMed Central  Google Scholar 

  • Li FY, Chaigne-Delalande B, Kanellopoulou C et al (2011) Signaling role for Mg(2+) revealed by immunodeficiency due to loss of MagT1. Nature 475:471–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lieu MT, Ng BG, Rush JS et al (2013) Severe, fatal multisystem manifestations in a patient with dolichol kinase-congenital disorder of glycosylation. Mol Genet Metab 110:484–489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Litchfield WJ, Wells WW (1978) Effect of galactose on free radical reactions of polymorphonuclear leukocytes. Arch Biochem Biophys 188:26–30

    Article  CAS  PubMed  Google Scholar 

  • Lübbehusen J, Thiel C, Rind N et al (2010) Fatal outcome due to deficiency of subunit 6 of the conserved oligomeric Golgi complex leading to a new type of congenital disorders of glycosylation. Hum Mol Genet 19:3623–3633

    Article  PubMed  CAS  Google Scholar 

  • Lübke T, Marquardt T, von Figura K, Körner C (1999) A new type of carbohydrate-deficient glycoprotein syndrome due to a decreased import of GDP-fucose into the golgi. J Biol Chem 274:25986–25989

    Article  PubMed  Google Scholar 

  • Lühn K, Marquardt T, Harms E, Vestweber D (2001) Discontinuation of fucose therapy in LADII causes rapid loss of selectin ligands and rise of leukocyte counts. Blood 97:330–332

    Article  PubMed  Google Scholar 

  • Lundin KE, Hamasy A, Backe PH et al (2015) Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene. Clin Immunol 161:366–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyons JJ, Milner JD, Rosenzweig SD (2015) Glycans instructing immunity: the emerging role of altered glycosylation in clinical immunology. Front Pediatr 3:54

    Article  PubMed  PubMed Central  Google Scholar 

  • Maratha A, Stockmann H, Coss KP et al (2016) Classical galactosemia: novel insights in IgG N-glycosylation and N-glycan biosynthesis. Eur J Hum Genet doi: 10.1038/ejhg.2015.254

  • Marquardt T, Brune T, Lühn K et al (1999a) Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism. J Pediatr 134:681–688

    Article  CAS  PubMed  Google Scholar 

  • Marquardt T, Lühn K, Srikrishna G, Freeze HH, Harms E, Vestweber D (1999b) Correction of leukocyte adhesion deficiency type II with oral fucose. Blood 94:3976–3985

    CAS  PubMed  Google Scholar 

  • 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). Nat Genet 16:88–92

    Article  CAS  PubMed  Google Scholar 

  • Metzker A, Eisenstein B, Oren J, Samuel R (1988) Tumoral calcinosis revisited—common and uncommon features. Report of ten cases and review. Eur J Pediatr 147:128–132

    Article  CAS  PubMed  Google Scholar 

  • Molinari F, Foulquier F, Tarpey PS et al (2008) Oligosaccharyltransferase-subunit mutations in nonsyndromic mental retardation. Am J Hum Genet 82:1150–1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monin ML, Mignot C, De Lonlay P et al (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 J Rare Dis 9:207

    Article  PubMed  PubMed Central  Google Scholar 

  • Morava E, Vodopiutz J, Lefeber DJ et al (2012) Defining the phenotype in congenital disorder of glycosylation due to ALG1 mutations. Pediatrics 130:e1034–1039

    Article  PubMed  Google Scholar 

  • Moremen KW, Trimble RB, Herscovics A (1994) Glycosidases of the asparagine-linked oligosaccharide processing pathway. Glycobiology 4:113–125

    Article  CAS  PubMed  Google Scholar 

  • Murali C, Lu JT, Jain M et al (2014) Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia. Mol Genet Metab Rep 1:213–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nasirikenari M, Segal BH, Ostberg JR, Urbasic A, Lau JT (2006) Altered granulopoietic profile and exaggerated acute neutrophilic inflammation in mice with targeted deficiency in the sialyltransferase ST6Gal I. Blood 108:3397–3405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noelle V, Knuepfer M, Pulzer F et al (2005) Unusual presentation of congenital disorder of glycosylation type 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema. Eur J Pediatr 164:223–226

    Article  PubMed  Google Scholar 

  • Ong BB, Gole GA, Robertson T, McGill J, de Lore D, Crawford M (2009) Retinal hemorrhages associated with meningitis in a child with a congenital disorder of glycosylation. Forensic Sci Med Pathol 5:307–312

    Article  PubMed  Google Scholar 

  • Pérez-Dueñas B, García-Cazorla A, Pineda M et al (2009) Long-term evolution of eight Spanish patients with CDG type Ia: typical and atypical manifestations. Eur J Paediatr Neurol 13:444–451

    Article  PubMed  Google Scholar 

  • Piton A, Redin C, Mandel JL (2013) XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. Am J Hum Genet 93:368–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pokrovskaya ID, Willett R, Smith RD, Morelle W, Kudlyk T, Lupashin VV (2011) Conserved oligomeric Golgi complex specifically regulates the maintenance of Golgi glycosylation machinery. Glycobiology 21:1554–1569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Priatel JJ, Chui D, Hiraoka N et al (2000) The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis. Immunity 12:273–283

    Article  CAS  PubMed  Google Scholar 

  • Ramaekers VT, Stibler H, Kint J, Jaeken J (1991) A new variant of the carbohydrate deficient glycoproteins syndrome. J Inherit Metab Dis 14:385–388

    Article  CAS  PubMed  Google Scholar 

  • Richard E, Vega AI, Pérez B et al (2009) Congenital disorder of glycosylation Ia: new differentially expressed proteins identified by 2-DE. Biochem Biophys Res Commun 379:267–271

    Article  CAS  PubMed  Google Scholar 

  • Rohlfing AK, Rust S, Reunert J et al (2014) ALG1-CDG: a new case with early fatal outcome. Gene 534:345–351

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Rymen D, Peanne R, Millón MB et al (2013) MAN1B1 deficiency: an unexpected CDG-II. PLoS Genet 9:e1003989

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rymen D, Winter J, Van Hasselt PM et al (2015) Key features and clinical variability of COG6-CDG. Mol Genet Metab 116:163–170

    Article  CAS  PubMed  Google Scholar 

  • Sadat MA, Moir S, Chun TW et al (2014) Glycosylation, hypogammaglobulinemia, and resistance to viral infections. N Engl J Med 370:1615–1625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saldova R, Stöckmann H, O’Flaherty R, Lefeber DJ, Jaeken J, Rudd PM (2015) N-glycosylation of serum IgG and total glycoproteins in MAN1B1 deficiency. J Proteome Res 14:4402–4412

    Article  CAS  PubMed  Google Scholar 

  • Sassi A, Lazaroski S, Wu G et al (2014) Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J Allergy Clin Immunol 133:1410–1419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott K, Gadomski T, Kozicz T, Morava E (2014) Congenital disorders of glycosylation: new defects and still counting. J Inherit Metab Dis 37:609–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serrano M, de Diego V, Muchart J et al (2015) Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment. Orphanet J Rare Dis 10:138

    Article  PubMed  PubMed Central  Google Scholar 

  • Shaheen R, Ansari S, Alshammari MJ et al (2013) A novel syndrome of hypohidrosis and intellectual disability is linked to COG6 deficiency. J Med Genet 50:431–436

    Article  CAS  PubMed  Google Scholar 

  • Silva Z, Konstantopoulos K, Videira PA (2012) The role of sugars in dendritic cell trafficking. Ann Biomed Eng 40:777–789

    Article  PubMed  Google Scholar 

  • Sparks SE, Krasnewich DM (2005) Congenital disorders of n-linked glycosylation pathway overview. In: Pagon RA, Adam MP, Ardinger HH et al (Eds.) GeneReviews. Seattle (WA): University of Washington, Seattle. Available from http://www.ncbi.nlm.nih.gov/books/NBK1332/

  • Sperandio M, Gleissner CA, Ley K (2009) Glycosylation in immune cell trafficking. Immunol Rev 230:97–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • \Stanley P, Guidos CJ (2009) Regulation of Notch signaling during T- and B-cell development by O-fucose glycans. Immunol Rev 230:201–15

    Article  CAS  PubMed  Google Scholar 

  • Stanley P, Schachter H, Taniguchi N et al (2009) N-Glycans. In: Varki A, Cummings R, Esko J (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  • Stibler H, Blennow G, Kristiansson B, Lindehammer H, Hagberg B (1994) Carbohydrate-deficient glycoprotein syndrome: clinical expression in adults with a new metabolic disease. J Neurol Neurosurg Psychiatry 57:552–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stray-Pedersen A, Backe PH, Sorte HS et al (2014) PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia. Am J Hum Genet 95:96–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strømme P, Maehlen J, Strøm EH, Torvik A (1991) Postmortem findings in two patients with the carbohydrate-deficient glycoprotein syndrome. Acta Paediatr Scand Suppl 375:55–62

    Article  Google Scholar 

  • 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(Pt 1):195–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Truin G, Guillard M, Lefeber DJ et al (2008) Pericardial and abdominal fluid accumulation in congenital disorder of glycosylation type Ia. Mol Genet Metab 94:481–484

    Article  CAS  PubMed  Google Scholar 

  • van de Kamp JM, Lefeber DJ, Ruijter GJ et al (2007) Congenital disorder of glycosylation type Ia presenting with hydrops fetalis. J Med Genet 44:277–280

    Article  PubMed  CAS  Google Scholar 

  • Van Dijk W, Brinkman-Van der Linden ECM, Havenaar EC (1998) Glycosylation of alpha1-acid glycoprotein (orosomucoid) in health and disease: occurrence, regulation and possible functional implications. Trens Glycosci Glycotechnol 10:235–245

    Article  Google Scholar 

  • Van Dijk W, Koeleman C, Van het Hof B, Poland D, Jakobs C, Jaeken J (2001) Increased alpha3-fucosylation of alpha(1)-acid glycoprotein in patients with congenital disorder of glycosylation type IA (CDG-Ia). FEBS Lett 494:232–235

    Article  PubMed  Google Scholar 

  • Van Schaftingen E, Jaeken J (1995) Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett 377:318–320

    Article  PubMed  Google Scholar 

  • Van Scherpenzeel M, Timal S, Rymen D et al (2014) Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency. Brain 137:1030–1038

    Article  PubMed  Google Scholar 

  • Varki A, Gagneux P (2012) Multifarious roles of sialic acids in immunity. Ann N Y Acad Sci 1253:16–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verma S, Bharti B, Inusha P (2010) Association of fungal sepsis and galactosemia. Indian J Pediatr 77:695–696

    Article  PubMed  Google Scholar 

  • Verstegen RH, Theodore M, van de Klerk H, Morava E (2012) Lymphatic edema in congenital disorders of glycosylation. JIMD Rep 4:113–116

    Article  PubMed  Google Scholar 

  • Videira PA, Amado IF, Crespo HJ et al (2008) Surface alpha 2-3- and alpha 2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis. Glycoconj J 25:259–68

    Article  CAS  PubMed  Google Scholar 

  • Vogt G, Chapgier A, Yang K et al (2005) Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations. Nat Genet 37:692–700

    Article  CAS  PubMed  Google Scholar 

  • Waggoner DD, Buist NR, Donnell GN (1990) Long-term prognosis in galactosaemia: results of a survey of 350 cases. J Inherit Metab Dis 13:802–818

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Hitchen PG, Panico M et al (2015) Glycoproteomic studies of IgE from a novel hyper IgE syndrome linked to PGM3 mutation. Glycoconj J doi: 10.1007/s10719-015-9638-y

  • Zhang Y, Yu X, Ichikawa M et al (2014) Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J Allergy Clin Immunol 133:1400–1409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the CDG-Professionals and Patients Association International Network (CDG- PPAIN) and Liliana Fellowship awarded to M. Monticelli. T. Ferro acknowledges Fundação para a Ciência e Tecnologia for the grant PD/BD/52472/2014 awarded to him.

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Authors and Affiliations

  1. Centro de Estudos de Doenças Crónicas, CEDOC, NOVA Medical School / Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal

    Maria Monticelli, Tiago Ferro & Paula A. Videira

  2. Dipartimento di Biologia, Università degli Studi di Napoli “Federico II”, Naples, Italy

    Maria Monticelli

  3. UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Caparica, Portugal

    Tiago Ferro & Paula A. Videira

  4. Portuguese Association for Congenital Disorders of Glycosylation (CDG), Lisbon, Portugal

    Vanessa dos Reis Ferreira

  5. CDG & Allies - Professionals and Patient Associations International Network (CDG & Allies - PPAIN), Caparica, Portugal

    Jaak Jaeken, Vanessa dos Reis Ferreira & Paula A. Videira

  6. Center for Metabolic Disease, KU Leuven, Leuven, Belgium

    Jaak Jaeken

Authors
  1. Maria Monticelli
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  2. Tiago Ferro
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  3. Jaak Jaeken
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  4. Vanessa dos Reis Ferreira
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  5. Paula A. Videira
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Corresponding authors

Correspondence to Vanessa dos Reis Ferreira or Paula A. Videira.

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Conflict of interests

Vanessa dos Reis Ferreira is President and founder of the Portuguese Association for CDG and other Rare Metabolic Diseases (APCDG-DMR). All other authors declare no competing financial interests.

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Communicated by: Eva Morava

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Monticelli, M., Ferro, T., Jaeken, J. et al. Immunological aspects of congenital disorders of glycosylation (CDG): a review. J Inherit Metab Dis 39, 765–780 (2016). https://doi.org/10.1007/s10545-016-9954-9

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  • DOI: https://doi.org/10.1007/s10545-016-9954-9

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