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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Biochim Biophys Acta. Author manuscript; available in PMC 2014 February 7.
Published in final edited form as:
PMCID: PMC3917312
NIHMSID: NIHMS551356

CDG nomenclature: Time for a change!

Congenital disorders of glycosylation (CDG) are a rapidly growing disease family with about 40 diseases reported since its first clinical description in 1980 [1]. The large majority of these are diseases of protein hypoglycosylation, but in recent years several defects in lipid glycosylation have also been identified [2,3]. Most protein glycosylation disorders are due to defects in the N-glycosylation pathway, the remaining ones affecting the O-glycosylation pathway or combined N-and O-glycosylation pathways. No defects in C-glycosylation have been detected yet. The first described CDG patients were shown to have an abnormal serum transferrin (Tf) isoelectrofocusing (IEF) pattern with increases in the di-and asialotransferrin fractions [4]. They were found to have deficient phosphomannomutase (PMM) activity [5] and mutations in the PMM2 gene [6]. PMM-deficient patients were designated as CDG-Ia. Subsequently, a patient was discovered with a serum Tf IEF pattern characterized by increases not only of the even (2 and 0) but also of the uneven (3 and 1) sialoTf bands [7]. Since these patterns were qualitatively different, we called the latter a type 2 pattern as opposed to the type 1 pattern seen in PMM deficiency. In the patient with the type 2 pattern, a deficiency was demonstrated to be in a Golgi glycosyltransferase, namely N-acetylglucosaminyltransferase II [8]. This disease was labeled CDG-IIa. New patients were classified as CDG-I or CDG-II according to the Tf IEF pattern, and each new defect took the next letter of the alphabet.

We presently count 14 CDG-I diseases (CDG-Ia up to CDG-In), and 8 CDG-II diseases (CDG-IIa up to CDG-IIh). Since this nomenclature is based on the Tf IEF pattern, it relates only to N-glycosylation diseases associated with deficient sialylation. Gradually it became clear that CDG-I defects were limited to defects in pre-ER or ER proteins whereas CDG-II defects were caused by defects in Golgi or Golgi-associated proteins. However, some of these disorders also show abnormal O-glycosylation such as the COG defects (review in [9]) and the V-ATPase defect in cutis laxa type II [10]. Also, it appeared that a patient with an alpha-glucosidase I deficiency in the ER had a normal Tf IEF pattern [11]. Still this patient was labeled as CDG-IIb, which is an inconsistency of this classification. For this reason and for a number of other reasons explained elsewhere [12], we strongly suggest that this nomenclature should be discontinued in favor of a transparent designation of glycosylation disorders and that it be applied to new and established types of CDG. We propose using only the official gene symbol (not in italics) followed by ‘-CDG’ (list of approved gene names at http://www.genenames.org). A classification of the known types of CDG, along with the traditional and new nomenclature, is shown in Table 1 (adapted from [12]).

Table 1
Proposed nomenclature for CDG (nomenclature to be superseded is included in italics and enclosed in parenthesis).a

References

1. Jaeken J, Vanderschueren-Lodeweyckx M, Casaer P, et al. Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG deficiency, increased serum arylsulfatase A and increased CSF protein: a new syndrome. Pediatr Res. 1980;14:179.
2. Freeze HH. Genetic defects in the human glycome. Nat Rev Genet. 2006;7:537–551. [PubMed]
3. Jaeken J, Matthijs G. Congenital disorders of glycosylation: a rapidly expanding disease family. Annu Rev Genomics Hum Genet. 2007;8:261–278. [PubMed]
4. Jaeken J, van Eijk HG, van der Heul C, Corbeel L, Eeckels R, Eggermont E. Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome. Clin Chim Acta. 1984;144:245–247. [PubMed]
5. Van Schaftingen E, Jaeken J. Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett. 1995;377:318–320. [PubMed]
6. Matthijs G, Schollen E, Pardon E, et al. Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome) Nat Genet. 1997;16:88–92. Erratum in Nat Genet 1997; 16: 316. [PubMed]
7. Ramaekers VT, Stibler H, Kint J, Jaeken J. A new variant of the carbohydrate deficient glycoproteins syndrome. J Inherit Metab Dis. 1991;14:385–388. [PubMed]
8. Jaeken J, Schachter H, Carchon H, De Cock P, Coddeville B, Spik G. Carbohydrate deficient glycoprotein syndrome type II: a deficiency in Golgi localised Nacetylglucosaminyltransferase II. Arch Dis Child. 1994;71:123–127. [PMC free article] [PubMed]
9. Zeevaert R, Foulquier F, Jaeken J, Matthijs G. Deficiencies in subunits of the conserved oligomeric Golgi complex define a novel group of Congenital Disorders of Glycosylation. Mol Genet Metab. 2008;93:15–21. [PubMed]
10. Kornak U, Reynders E, Dimopoulou A, et al. Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. Nat Genet. 2008;40:32–34. [PubMed]
11. De Praeter CM, Gerwig GJ, Bause E, et al. A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency. Am J Hum Genet. 2000;66:1744–1756. [PubMed]
12. Jaeken J, Hennet T, Freeze H, Matthijs G. On the nomenclature of Congenital Disorders of Glycosylation (CDG) J Inherit Metab Dis. 2008;31:669–672. [PubMed]