CDG2I belongs to a group of phenotypically and genetically heterogeneous Congenital Disorders of Glycosylation (CDGs) caused by enzymatic defects in the synthesis and processing of glycans or oligosaccharides on glycoproteins. While type 1 CDGs involve defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, type 2 CDGs are a result of defects in the trimming and processing of the protein-bound glycans either in the endoplasmic reticulum or the Golgi apparatus.

CDG2I is characterized by intellectual disability, developmental delay, atrophy of the cerebellum and brain stem, truncal ataxia and hypotonia. Affected patients exhibit decreased O-glycosylation of APOC3 and decreased N-glycosylation of serum transferrin and alpha-1-acid glycoprotein. The disorder affects both men and women equally. However, the exact prevalence of this condition is yet to be determined.

Diagnosis of CDG2I is done by isoelectric focusing, which allows the detection of abnormal transferrin patterns. Currently, enzyme replacement therapy is being investigated as a possible treatment for CDG. Patients also require symptomatic support and may benefit from physical, occupational and speech therapy. 

The disorder follows an autosomal recessive pattern of inheritance and is caused by mutations in the COG5 gene. COG5 is involved in the intra-Golgi and ER to Golgi vesicle-mediated transport of proteins, particularly the enzymes responsible for glycosylation. At least 8 mutations in the COG5 gene have been identified to result in CDG2I. The homozygous intronic transition 1669-15T-C results in altered splicing and a transcript lacking the 58 amino acids of exons 15 and 16.