Clinical Information

Congenital disorders of glycosylation (CDG) are a group of over 150 inherited metabolic disorders largely affecting N- and O-glycosylation of proteins. The majority of CDG are attributed to congenital defects in N-glycosylation, which take place primarily in the cytoplasm and in the membranes of the endoplasmic reticulum. O-glycosylation defects are frequently tissue specific and present differently than classic N-linked defects. CDG are currently classified into 2 main groups. Type I CDG is characterized by defects in the assembly or transfer of the dolichol-linked glycan (sugar chain), while type II involves processing defects of the glycan. Depending on the specific defect, an N-glycosylation disorder can be either a type I or type II CDG.

N-linked CDG are phenotypically diverse, usually presenting as clinical syndromes with multisystemic involvement and a broad clinical spectrum. There is considerable variation in the severity of this group of diseases ranging from a mild presentation in adults to severe multi-organ dysfunction causing infantile lethality. Intellectual disability is common, although in some subtypes, phosphomannose isomerase-CDG (MPI-CDG or CDG type Ib) in particular, intellect is preserved. CDG should be considered in all patients with multisystem disease and in those with neurologic abnormalities, including developmental delay and seizures; brain abnormalities, such as cerebellar atrophy or hypoplasia; and unexplained liver dysfunction. Additional common symptoms that may be present include abnormal subcutaneous fat distribution; gastrointestinal issues, such as vomiting, chronic diarrhea, and protein-losing enteropathy; eye abnormalities, including retinal degeneration and strabismus; and cardiomyopathy.

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of released N-linked oligosaccharides, as performed in this assay, is a global assessment of N-linked glycosylation. This complements the also performed transferrin and apolipoprotein CIII isoform analysis (see CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum) by providing additional information on specific structural oligosaccharide abnormalities that can guide molecular testing.