The glycans on proteins are either N-linked (to the amide group of asparagine via an N-acetylglucosamine residue) or O-linked (to the hydroxyl group of serine or threonine via an N-acetylgalactosamine or a xylose residue).
The first patients with a CDG were reported in 1980 (78). Since then, investigators have discovered deficiencies in N-glycan assembly, in N-glycan processing, in O-glycan assembly, in glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, in multiple glycosylation and other pathways. A combination of N- and O-glycosylation defect is also possible. Most glycosylation disorders are severe, multisystem disease, underlining the extremely important biological roles of glycans.
Nomenclature Full article: CDG Nomenclature: Time for a change
A new nomenclature of CDG (Congenital Disorders of Glycosylation) is proposed because the current one is too complex for clinicians and provides no added value.
It is now more than 10 years since J.Jaeken introduced a classification for CDG (CDG Ia etc., CDG IIa etc.) essentially on the basis of the serum transferrin pattern obtained by isoelectrofocusing (Jaeken et al 1994). A nomenclature system that essentially (sub)classified the different types of CDG alphabetically was proposed by the participants of the First International workshop on CDG and related disorders, in Leuven in 1999, and widely announced (Aebi et al 1999; Matthijs 2000; Participants 2000). We think that time has come to reconsider this matter.
More specifically, it is our strong feeling that the current classification should be discontinued for a number of reasons.
1. The number of CDG has increased tremendously. Since the first description of patients, some 40 types of CDG (including protein and lipid glycosylation defects) have been discovered (Jaeken and Matthijs 2007;
Freeze 2007). There is every reason to believe that this will continue for many years, since at least 200 genes seem to be involved in glycosylation! This large number of CDG makes the classification extremely complex, particularly for the metabolic and other clinicians who have to use it in their daily practice. Moreover, since this classification is alphabetically and chronologically by the order of discovery, it provides no added value since it does not refer to real biological features such as enzymes or genes. Thus, it only complicates the recognition and recall of the basic defect.
2. That there is no need for this classification is well illustrated by the CDG due to an O-glycosylation defect. These are not included in this classification and have 'popular' names and/or 'biochemical' names that are informative about the nature of the disease (e.g. muscle-eye-brain disease or POMT defect, hereditary multiple exostoses, familial tumoral calcinosis...).
3. Even if it were decided to continue this classification, it would be extremely difficult to imagine how to proceed further in this way. It would bring us into insurmountable difficulties. How do we classify the upcoming disorders of dolichol biosynthesis (Kranz et al 2007), the lipid glycosylation disorders (Simpson et al 2004) and so on?
Our suggestion is to keep (of course) Congenital Disorders of Glycosylation (CDG) as an umbrella name for all protein glycosylation disorders and to extend it to the lipid glycosylation disorders. To indicate the specific disorder, we propose to make obligatory the use of the gene name. But in parallel, the name of the protein (enzyme, transporter, chaperone, ...) may be used (abbreviated or not; this may be a 'trivial' name: e.g. CDG due to mannosyltransferase VIII deficiency instead of dolichol-P-Man:Man7Glc-NAc2-PP-dolichol mannosyltransferase deficiency). In a transition period the 'old' nomenclature can be included in brackets as that nomenclature is gradually replaced. We propose to add the '-CDG' after the gene name: e.g. PMM2-CDG.
As long as the primary (genetic) defect is unknown for a specific type, we will continue to call the disease CDG-x; hence, this group constitutes a series of cases and patients 'to be solved'.
Classification of Congenital Disorders of Glycosylation with the novel nomenclature as of 2009. Last updated 12 Nov 2009.
- Table 1: Defects in protein N-glycosylation
- Table 2: Defects in protein O-glycosylation
- Table 3: Defects in glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation
- Table 4: Defects in multiple glycosylation and other pathways