Congenital Disorder Of Glycosylation, Type Iii

A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type IIi (CDG IIi, CDG2I) is caused by homozygous mutation in the COG5 gene (606821) on chromosome 7q22.

For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066).

Clinical Features

Paesold-Burda et al. (2009) described a 14-year-old Iraqi girl, born to remotely consanguineous parents, who at age 8 years demonstrated moderate mental retardation with slow and inarticulate speech, truncal ataxia, and mild hypotonia. Brain MRI revealed pronounced atrophy of the cerebellum and brainstem. Speech and cognition improved over the next several years, but mild hypotonia and ataxia persisted. Biochemical analysis showed decreased N-glycosylation of serum transferrin and alpha-1-acid glycoprotein, as well as decreased O-glycosylation of apolipoprotein C-III (APOC3; 107720). Retrograde Golgi-to-endoplasmic reticulum trafficking was markedly delayed in the patient fibroblasts upon brefeldin-A treatment, which is a hallmark of COG deficiency. The trafficking delay could be restored to normal values by expressing a wildtype COG5 cDNA in the patient cells. Paesold-Burda et al. (2009) suggested that CDG should be considered when investigating the basis of even mild neurologic impairments in children.

Molecular Genetics

In an Iraqi girl with a congenital disorder of glycosylation, Paesold-Burda et al. (2009) identified a homozygous intronic substitution (606821.0001) leading to exon skipping and severely reduced expression of the COG5 protein.