Glycoproteins play important roles in many biological functions, including growth, differentiation, organ development, signal transduction, and immunological defences. Congenital disorders of glycosylation (CDGs) constitute a diverse spectrum of inheritable metabolic anomalies characterized by hypoglycosylation of proteins and lipids. These disorders arise from genetic defects disrupting the intricate process of glycosylation, a post-translational modification crucial for the proper folding, stability, and function of critical biomolecules.
Defects in protein glycosylation can be broadly categorized into three groups:
• N-glycosylation: Targeting asparagine residues on the protein backbone.
• O-glycosylation: Modifying serine and threonine residues on the protein side chains.
• Combined N- and O-glycosylation: Affecting both N- and O-linked glycosylation pathways.
Pathogenic variations in the MAN1B1 gene affect the N-glycosylation of the protein and disrupt the Golgi’s overall morphology and functions.
Screening for N-glycosylation defects often employs the sensitive technique of serum transferring isoelectrofocusing. This method reveals distinct electrophoretic patterns, enabling differential diagnosis of CDG subtypes:
• Type 1 pattern signifies defects in glycan assembly and transfer, typically involving malfunctions in the cytosol and endoplasmic reticulum, characteristic of CDG-I.
• Type 2 pattern suggests processing defects within the Golgi apparatus, a hallmark of CDG-II.
Among CDG-II, MAN1B1-CDG is one of the more frequent, with over 40 described cases reported in the literature.
MAN1B1