A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants. The most common sub-type is PMM2-CDG (formally known as CDG-Ia) where the genetic defect leads to the loss of phosphomannomutase 2 (PMM2), the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate. Presentation
The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver disease; coagulopathies; failure to thrive (FTT); dysmorphic features (e.g., inverted nipples and subcutaneous fat pads), pericardial effusion, and hypotonia. If an MRI is obtained; cerebellar hypoplasia is a common finding.Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, peripheral neuropathy (PN), strabismus, nystagmus, optic disc pallor, and reduced rod function on electroretinography.Three subtypes PMM2-CDG, PMI-CDG, ALG6-CDG can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy. N-Glycosylation and known defects
A biologically very important group of carbohydrates is the asparagine (Asn)-linked, or N-linked, oligosaccharides. Their biosynthetic pathway is very complex and involves a hundred or more glycosyltransferases, glycosidases, transporters and synthases. This plethora allows for the formation of a multitude of different final oligosaccharide structures, involved in protein folding, intracellular transport/localization, protein activity, and degradation/half-life.
CDG-Ia = PMM2-CDG, CDG-Ib = PMI-CDG, CDG-Ic = ALG6-CDG etc.). The reason for the new nomenclature was the fact that proteins not directly involved in glycan synthesis (such as members of the COG-family and vesicular H+-ATPase) were found to be causing the glycosylation defect in some CDG patients. Also, defects disturbing other glycosylation pathways than the N-linked one are included in this classification. Examples are the α-dystroglycanopathies (e.g. POMT1/POMT2-CDG (Walker-Warburg syndrome and Muscle-Eye-Brain syndrome)) with deficiencies in O-mannosylation of proteins; O-xylosylglycan synthesis defects (EXT1/EXT2-CDG (hereditary multiple exostoses) and B4GALT7-CDG (Ehlers-Danlos syndrome, progeroid variant)); O-fucosylglycan synthesis (B3GALTL-CDG (Peters plus syndrome) and LFNG-CDG (spondylocostal dysostosis III)). Type I
Type I disorders involve disrupted synthesis of the lipid-linked oligosaccharide precursor (LLO) or its transfer to the protein.Types include:

Type II
Type II disorders involve malfunctioning trimming/processing of the protein-bound oligosaccharide chain.Types include:

Disorders of O-mannosylation
Disorders with deficient α-dystroglycan O-mannosylation.Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.Most common severe types include:

Treatment
No treatment is available for most of these disorders. Mannose supplementation relieves the symptoms in MPI-CDG for the most part, even though the hepatic fibrosis may persist. Fucose supplementation has had a partial effect on some SLC35C1-CDG patients.