Screening for N-linked congenital disorders of glycosylation
Providing information on specific structural oligosaccharide abnormalities to potentially direct further genetic testing
Congenital disorders of glycosylation (CDG) comprise a large group of inborn errors of metabolism affecting predominantly N- and O-glycosylation of proteins.
N-linked CDG commonly present as clinical syndromes with multisystemic involvement and a broad clinical spectrum.
In addition to transferrin and apolipoprotein CIII isoform analysis, this test also detects and analyzes serum N-linked oligosaccharides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for a more comprehensive evaluation of CDG.
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
CDG | CDG, S | Yes | Yes |
When this test is ordered, carbohydrate deficient transferrin for congenital disorders will always be performed at an additional charge.
For more information see Congenital Disorders of Glycosylation: Screening Algorithm.
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS)
Carbohydrate Deficient Glycoprotein Syndrome (CDGS)
CDG (Congenital Disorders of Glycosylation)
N-linked Glycosylation Disorders
N-glycan
N-linked glycosylation
N-linked oligosaccharides
N glycosylation
Glycoprotein
When this test is ordered, carbohydrate deficient transferrin for congenital disorders will always be performed at an additional charge.
For more information see Congenital Disorders of Glycosylation: Screening Algorithm.
Serum
This test is for congenital disorders of glycosylation. For evaluation of alcohol abuse, order CDTA / Carbohydrate Deficient Transferrin, Adult, Serum.
1. Patient’s age is required.
2. Reason for testing is required.
Question ID | Description | Answers |
---|---|---|
BG712 | Reason for Referral |
Developmentally delayed Congenital disorders of glycosylation Follow-up of known patient with CDG Evaluation of alcohol abuse - change test to 82425 (CDTA) Carb Def Transferrin, Adult, S |
Collection Container/Tube:
Preferred: Red Top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 0.15 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
1. Congenital Disorders of Glycosylation (CDG, CDGN, OLIGU) Patient Information
2. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
0.1 mL
Gross hemolysis | Reject |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Refrigerated (preferred) | 28 days | |
Frozen | 45 days | ||
Ambient | 7 days |
Screening for N-linked congenital disorders of glycosylation
Providing information on specific structural oligosaccharide abnormalities to potentially direct further genetic testing
Congenital disorders of glycosylation (CDG) comprise a large group of inborn errors of metabolism affecting predominantly N- and O-glycosylation of proteins.
N-linked CDG commonly present as clinical syndromes with multisystemic involvement and a broad clinical spectrum.
In addition to transferrin and apolipoprotein CIII isoform analysis, this test also detects and analyzes serum N-linked oligosaccharides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for a more comprehensive evaluation of CDG.
When this test is ordered, carbohydrate deficient transferrin for congenital disorders will always be performed at an additional charge.
For more information see Congenital Disorders of Glycosylation: Screening Algorithm.
Congenital disorders of glycosylation (CDG) are a group of over 100 inherited metabolic disorders largely affecting N- and O-glycosylation of proteins. Almost 50 inborn errors of metabolism are attributed to congenital defects in N-glycosylation, which takes place primarily in the cytoplasm and in the membranes of the endoplasmic reticulum. O-glycosylation defects are commonly 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, commonly 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 (MPI)-CDG (CDG-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 as well as 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) analysis of released N-linked oligosaccharides, as is 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.
Interpretative comment only.
The results of the transferrin and apolipoprotein CIII isoform analysis are followed up with matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) analysis of released N-linked oligosaccharides to assess N-linked glycosylation. Reports of abnormal results will include recommendations for additional biochemical and molecular genetic studies to identify more precisely the specific congenital disorder of glycosylation. Treatment options, the name and telephone number of contacts who may provide studies, and a telephone number for one of the laboratory directors (if the referring physician has additional questions) will be provided.
No significant cautionary statements
1. Sparks SE, Krasnewich DM. Congenital disorders of N-linked glycosylation and multiple pathway overview. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2005. Updated January 12, 2017. Accessed May 25, 2023. Available at: www.ncbi.nlm.nih.gov/books/NBK1332/
2. Chang IJ, He M, Lam CT. Congenital disorders of glycosylation. Ann Transl Med. 2018;6(24):477. doi:10.21037/atm.2018.10.45
3. Francisco R, Marques-da-Silva D, Brasil S, et al. The challenge of CDG diagnosis. Mol Genet Metab. 2019;126(1):1-5. doi:10.1016/j.ymgme.2018.11.003
4. Freeze HH, Chong JX, Bamshad MJ, Ng BG. Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am J Hum Genet. 2014;94(2):161-175. doi:10.1016/j.ajhg.2013.10.024
5. Scott K, Gadomski T, Kozicz, Morava E. Congenital disorders of glycosylation: new defects and still counting. J Inherit Metab Dis. 2014;37(4):609-617. doi:10.1007/s10545-014-9720-9
N-linked oligosaccharides are enzymatically released, purified, and then detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.(Unpublished Mayo method)
Wednesday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
83789
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
CDGN | CDGN, S | In Process |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
602577 | Interpretation | 59462-2 |
BG712 | Reason for Referral | 42349-1 |
602576 | Reviewed By | 18771-6 |
Change Type | Effective Date |
---|---|
Test Status - Test Resumed | 2022-02-08 |
Test Changes - Specimen Information | 2022-01-26 |
Test Status - Test Delay | 2022-01-21 |