Disorders of Multiple Glycosylation and Other Pathways

Disorders of Multiple Glycosylation and Other Pathways

CD BioGlyco has many state-of-the-art technology platforms including Glyco™ Synthesis Platform, Glycoproteomics Platform, Glycobiology Microarray Platform, Glycoengineering Platform, and Glycosylation Site-specific Antibody-Drug Conjugate (ADC) Development Platform. These platforms of CD BioGlyco provide clients with an assurance of disorders of multiple glycosylation and other pathways-related studies

Overview of Disorders of Multiple Glycosylation and Other Pathways

Many of the defects in previous congenital disorders of glycosylation (CDG) nomenclature are not actually restricted to the N- or O-glycosylation pathway; their manifestation is due to defects in other pathways involved in carbohydrate metabolism. CMP-sialic acid transporter protein (SLC35A1) deficiency along with CDG-IIf and GDP-rock sugar transporter protein (SLC35C1) are examples of proteins that affect multiple glycosylation pathways. DK1-CDG (CDG-Im) is also a good example, as polyterpenes alcohol kinase 1 provides substrates for N- and O-linked glycans, GPI anchors, and C- and O-mannose basylation, and impairs multiple pathways in this way. To date, defects of multiple glycosylation and other pathways include 17 defects, some of which are briefly described next.


The conserved oligomeric Golgi (COG) complex is a large eight-subunit (Cog1-Cog8) complex that plays a key role in protein transport between the ER and Golgi and within the Golgi apparatus. The complex is divided into two substructures; lobe A contains Cog 2-4 and lobe B Cog 5-7, while Cog1 and Cog8 bridge these lobes. In addition, cutaneous laxity syndrome, a rare skin disorder characterized by skin wrinkling due to defects in the synthesis of elastic fibers and other proteins of the extracellular matrix, has been described as COG7-CDG. Common features of COG-CDG are dysmorphism, hypotonia, feeding problems, growth retardation, and brain atrophy. The COG complex may involve not only glycosylation but also other cellular functions, and therefore the term "CDG-plus" has been proposed for the COG defect.

  • ATP6V0A2-CDG

This disease can be considered another "CDG-plus" defect. Although laboratory findings of transferrin isoelectric focusing (Tf-IEF) type 2 pattern, abnormal isoelectric focusing of apolipoprotein C-III (apoC-III) and abnormal mass spectrometry of total serum proteoglycans can be attributed to defects in the classical CDG type II enzymes involved in glycan processing, the cause of disrupted glycosylation is a defect in the α-subunit of the vesicular ATPase H+-pump. It seems that the disturbed H+ concentration in the vesicles affects the correct processing of glycans. All patients had generalized skin laxity at birth, but ophthalmic abnormalities and motor retardation that improved with age were also described.

  • SLC35C1-CDG (CDG-IIc)

This disorder, also known as type II leukocyte adhesion deficiency (LAD II) syndrome (CDG-IIc), is caused by a deficiency in the GDP-fucose transporter protein (SLC35C1), resulting in a lack of fucosylated selectin ligands, which leads to developmental defects and immunodeficiency. Patients with SLC35C1-CDG also exhibit intense mental and growth retardation.


B4GALT1-CDG has been described as deficient in β1,4-galactosyltransferase. The typical clinical manifestations are Dandy-Walker malformation and myopathy. MALDI analysis of transferrin N-linked glycans revealed the presence of species lacking terminal sialic acid and galactose residues.

Simplified scheme of the cytosolic and ER part of the N-glycosylation pathway.Fig.1 Simplified scheme of the cytosolic and ER part of the N-glycosylation pathway. (Grünewald, et al, 2002)

Description of Disorders of Multiple Glycosylation and Other Pathways

Glycosylation is the process by which an enzyme (glycosyltransferase) transfers monosaccharides (monosaccharides) to molecules (such as proteins, lipids, or other sugars). Glycosylation can be divided into N-glycosylation, O-glycosylation, glycosylphosphatidylinositol (GPI) -anchored biosynthesis, and lipid glycosylation. All glycosylation pathways require high-energy forms of monosaccharides (called active sugars) or enzymes to be able to transfer monosaccharides to proteins, lipids, or glycans. These active sugars are usually monosaccharides, linked to a group of molecules called nucleosides (nucleotide sugars), or linked to lipid polyols through high-energy phosphate bonds. After the first monosaccharide is linked to lipids, proteins, or sugars, other monosaccharides can be transferred to the linked monosaccharides in turn to form sugar chains, called glycans. Since glycosylation can occur in different locations of the cell, such as cytosol, endoplasmic reticulum (ER), or Golgi, there is a transport system to transport different glycosylation components (such as enzymes and active sugars) to the right location.

The disorder of the glycosylation pathway is caused by the common component defects between different glycosylation pathways, which may include enzymes, sugars, and transport systems. These glycosylation pathway barriers can be broken down into the following six categories.

Carbohydrate & Disease is an important topic in the field of glycoscience. CD BioGlyco is willing to be the partner of customers in this field. We provide comprehensive services including but not limited to Custom Monosaccharide Synthesis, Custom Glycoconjugate Synthesis, Custom Complex N-linked Oligosaccharides Synthesis, Custom Monosaccharide Synthesis, and Monosaccharides-based Glycomedicine Development. For further details, please don't hesitate to contact us.


  1. Grünewald, S.; et al. Congenital disorders of glycosylation: a review. Pediatric research. 2002, 52(5): 618-624.
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