Clinical Information

Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndrome, are a group of over 75 inherited metabolic disorders affecting several steps of the pathway involved in the glycosylation of proteins. 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, while type II involves processing defects of the glycan. Apolipoprotein CIII (Apo-CIII) isoforms, a protein with a single core 1 mucin type O-glycosylate protein, is a complementary evaluation for the CDG type II profile. This analysis will evaluate mucin type O-glycosylation, a defect that happens in the Golgi apparatus, and will change the ratios, increasing the asialo or monoisalo forms and decreasing the fully sialilate (disialo) forms.

CDG typically present as multisystemic disorders with a broad clinical spectrum including developmental delay, hypotonia, with or without neurological abnormalities, abnormal magnetic resonance imaging findings, skin manifestations, and coagulopathy. There is considerable variation in the severity of this group of diseases ranging from a mild presentation in adults to severe multiorgan dysfunctions causing infantile lethality. In some subtypes, MPI-CDG (CDG-Ib) in particular, intelligence is not compromised. CDG should be suspected in all patients with neurological abnormalities including developmental delay and seizures, brain abnormalities such as cerebellar atrophy or hypoplasia as well as unexplained liver dysfunction. Abnormal subcutaneous fat distribution and chronic diarrhea each may or may not be present. The differential diagnosis of abnormal transferrin patterns also includes liver disease not related to CDG including uncontrolled galactosemia, hereditary fructose intolerance in acute crisis, and liver disease of unexplained etiology.

Transferrin and apolipoprotein CIII isoform analysis test is the initial screening test for CDG. The results of the transferrin and apolipoprotein CIII isoform analysis should be correlated with the clinical presentation to determine the most appropriate follow-up testing strategy including enzyme, molecular, and research-based testing. Enzymatic analysis for phosphomannomutase and phosphomannose isomerase in leukocytes (PMMIL / Phosphomannomutase [PMM] and Phosphomannose Isomerase [PMI], Leukocytes) or fibroblasts (PMMIF / Phosphomannomutase [PMM] and Phosphomannose Isomerase [PMI], Fibroblasts) should be performed if either PMM2-CDG (CDG-Ia) or MPI-CDG (CDG-Ib) are suspected.