Carbohydrate Deficient Glycoprotein Syndrome (CDGS), CDG (Congenital Disorders of Glycosylation), CDGS (Carbohydrate Deficient Glycoprotein Syndrome), CDT (Carbohydrate Deficient Transferrin), Congenital Disorders of Glycosylation (CDG), Glycoprotein Syndrome, Carbohydrate Deficient, Transferrin for Carbohydrate Deficient Transferrin (CDT), Transferrin Isoforms
This testing is used to screen patients for suspected congenital disorders of glycosylation (N- and O-glycosylation defects as well as glycan structure analysis).
Congenital disorders of glycosylation (CDG) encompass over 150 genetic conditions spanning a broad clinical spectrum.
The main CDG profiles that can be identified by this analysis are type I, some type II, and mixed type CDG.
1. Patient's age is required.
2. Reason for testing is required.
Other conditions such as acute crisis of hereditary fructose intolerance, galactosemia, substance abuse, and acute liver disease may have a congenital disorders of glycosylation (CDG) profile that is indistinguishable from any other true CDG type I cases. Relevant clinical information and the indication for the analysis should be provided with the specimen.
Transferrin glycosylation patterns may normalize so repeat testing is warranted in patients with significant clinical suspicion.
Positive test results could be due to a genetic or nongenetic condition; additional confirmatory testing is required.
In serum, the bi-antennary transferrin (di-oligo) fraction is the most abundant transferrin isoform. Congenital disorders of glycosylation (CDG)-I generally shows increases in mono-oligo- and/or a-oligo transferrin isoforms whereas CDG-II shows elevated increased transferrin with truncated glycans of varying degree depending on the type of defect.(1)
Results are reported as the mono-oligosaccharide/di-oligosaccharide transferrin ratio, the a-oligosaccharide/di-oligosaccharide transferrin ratio, the tri-sialo/di-oligosaccharide transferrin ratio, and the apolipoprotein CIII-1/apolipoprotein CIII-2 ratio, and the apolipoprotein CIII-0/apolipoprotein CIII-2 ratio. The report will include the quantitative results and an interpretation.
The congenital disorders of glycosylation (CDG) profiles are can be categorized into 5 types:
1. CDG type I profile. Mono-oligosaccharide/di-oligosaccharide transferrin ratio and/or the a-oligosaccharide/di-oligosaccharide transferrin ratio are abnormal. This group should have the apolipoprotein C-III profile within the normal ranges, because the Golgi system is not affected in CDG type I.
2. CDG type II profile. The tri-sialo/di-oligosaccharide transferrin ratio is abnormal. In this category, the apolipoprotein C-III profile will have 2 scenarios:
A. The apolipoprotein CIII-1/apolipoprotein CIII-2 ratio and/or the apolipoprotein CIII-0/apolipoprotein CIII-2 ratio will be abnormal. In this case, the defect is most likely glycan processing in the Golgi apparatus; therefore, a CDG (conserved oligomeric Golgi [COG]) defect or defect that alters the Golgi apparatus is likely.
B. The apolipoprotein CIII-1/apolipoprotein CIII-2 ratio and/or the apolipoprotein CIII-0/apolipoprotein CIII-2 ratio are normal. In this case, most likely the defects do not involve the Golgi system, thus the molecular defect is different.
3. CDG mixed type profile (type I and II together). In this type of profile one can have abnormal tri-sialo/di-oligosaccharide transferrin ratio with the mono-oligosaccharide/di-oligosaccharide transferrin ratio and/or the a-oligosaccharide/di-oligosaccharide transferrin ratio abnormal, and may have the apolipoprotein CIII-1/apolipoprotein CIII-2 ratio and the apolipoprotein CIII-0/apolipoprotein CIII-2 ratio normal or abnormal, depending if the defects involve Golgi apparatus.
4. CDG with normal transferrin and apolipoprotein profile. Some CDG (eg, PGM3, some ALG13, MOGS, NGLY1, SLC35C1, Fut8) pose a problem for their detection. Thus, a careful medical history, physical exam, and analysis of other protein status may be informative for general protein glycosylation defects. If suspicious for either NGLY1- or MOGS-CDG, specific oligosaccharides in urine can be detected (OLIGU / Oligosaccharide Screen, Random, Urine).
5. When the profile cannot be categorized following the above classification, the abnormalities will be reported descriptively according to the molecular mass of the glycan isoform structures.
Reports of abnormal results will include recommendations for additional biochemical and molecular genetic studies to more precisely identify the correct form of CDG. If applicable, treatment options, the name and telephone number of contacts who may provide studies at Mayo Clinic or elsewhere, and a telephone number for one of the laboratory directors (if the referring physician has additional questions) will be provided.