Test Catalog

Test Id : CDG

Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Screening for congenital disorders of glycosylation

 

This test is not useful for screening patients for chronic alcohol abuse.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Suggested Testing Strategy:

 

Disorder

Target

Mayo Test ID

N-glycan, core 1 mucin type O-glycosylation, and conserved oligomeric Golgi (COG) complex defects

Transferrin, apolipoprotein CIII

CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum

N-glycan, core 1 mucin type O-glycosylation, and COG complex defects

Serum total N-linked glycans, transferrin, and apolipoprotein CIII

CDGN / Congenital Disorders of N-Glycosylation, Serum (includes test ID CDG)

Stepwise analysis of transferrin, apolipoprotein CIII, and serum total N-glycans

alpha-Dystroglycanopathies

Genes: DAG1, FKRP, FKTN, ISPD, LARGE1, POMGNT1, POMGNT2, POMT1, POMT2

CDGGP / Congenital Disorders of Glycosylation Gene Panel, Varies

 

For more information, see Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Affinity Chromatography-Mass Spectrometry (MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CDG, S

Aliases
Lists additional common names for a test, as an aid in searching

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

Carbohydrate Deficient Glycoprotein Syndrome (CDGS)

Apolipoprotein CIII

Apo-CIII

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Suggested Testing Strategy:

 

Disorder

Target

Mayo Test ID

N-glycan, core 1 mucin type O-glycosylation, and conserved oligomeric Golgi (COG) complex defects

Transferrin, apolipoprotein CIII

CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum

N-glycan, core 1 mucin type O-glycosylation, and COG complex defects

Serum total N-linked glycans, transferrin, and apolipoprotein CIII

CDGN / Congenital Disorders of N-Glycosylation, Serum (includes test ID CDG)

Stepwise analysis of transferrin, apolipoprotein CIII, and serum total N-glycans

alpha-Dystroglycanopathies

Genes: DAG1, FKRP, FKTN, ISPD, LARGE1, POMGNT1, POMGNT2, POMT1, POMT2

CDGGP / Congenital Disorders of Glycosylation Gene Panel, Varies

 

For more information, see Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm.

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

This test is for congenital disorders of glycosylation. If the ordering provider is looking for evaluation of alcohol abuse, order CDTA / Carbohydrate Deficient Transferrin, Adult, Serum.

 

If either PMM2-CDG (CDG-Ia) or MPI-CDG (CDG-Ib) is suspected, order PMMIL / Phosphomannomutase and Phosphomannose Isomerase, Leukocytes.

Necessary Information

1. Patient's age is required.

2. Reason for testing is required.

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
BG160 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

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 0.1 mL

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. Biochemical Genetics Patient Information (T602)

2. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.05 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 45 days
Refrigerated 28 days
Ambient 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Screening for congenital disorders of glycosylation

 

This test is not useful for screening patients for chronic alcohol abuse.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

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.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Suggested Testing Strategy:

 

Disorder

Target

Mayo Test ID

N-glycan, core 1 mucin type O-glycosylation, and conserved oligomeric Golgi (COG) complex defects

Transferrin, apolipoprotein CIII

CDG / Carbohydrate Deficient Transferrin for Congenital Disorders of Glycosylation, Serum

N-glycan, core 1 mucin type O-glycosylation, and COG complex defects

Serum total N-linked glycans, transferrin, and apolipoprotein CIII

CDGN / Congenital Disorders of N-Glycosylation, Serum (includes test ID CDG)

Stepwise analysis of transferrin, apolipoprotein CIII, and serum total N-glycans

alpha-Dystroglycanopathies

Genes: DAG1, FKRP, FKTN, ISPD, LARGE1, POMGNT1, POMGNT2, POMT1, POMT2

CDGGP / Congenital Disorders of Glycosylation Gene Panel, Varies

 

For more information, see Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Glycosylation is the post-translational modification of proteins and lipids by the addition of glycans (sugars and sugar chains) in a complex stepwise fashion in the endoplasmic reticulum, Golgi apparatus, cytosol and sarcolemmal membrane. Congenital disorders of glycosylation (CDG) are a group of over 150 inherited metabolic disorders characterized by abnormal protein and lipid glycosylation. There are 2 main groups of CDG: type I, characterized by defects in the assembly or transfer of the dolichol-linked glycan in either the cytosol or endoplasmic reticulum (ER) and type II, involving processing defects of the glycan in the ER and Golgi apparatus. In addition, there are 2 categories of glycosylation: N-glycosylation where N-linked glycans are attached to a protein backbone via an asparagine residue on the protein, and O-glycosylation where O-glycans are attached to the hydroxyl group of threonine or serine. Apolipoprotein CIII (Apo-CIII) isoforms, 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 involving the Golgi apparatus, which is detected biochemically by the change in ratios of the 3 isoforms.

 

CDG typically present as multi-systemic disorders with a broad clinical spectrum including, but not limited to, 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 and children to severe multi-organ dysfunctions causing infantile lethality. In some subtypes, phosphomannose isomerase-CDG (MPI-CDG or 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 galactosemia, hereditary fructose intolerance in acute crisis, and liver disease of unexplained etiology.

 

Transferrin and apolipoprotein CIII isoform analysis are the initial screening tests 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 and Phosphomannose Isomerase, Leukocytes) should be performed if either PMM2-CDG (CDG-Ia) or MPI-CDG (CDG-Ib) is suspected.

 

Other glycosylation pathways, in addition to N- and O-glycosylation, have been elucidated, in particular, glycophosphatidylinositol (GPI)-anchored protein glycosylation disorders in which there is absent or decreased expression of all the GPI-linked antigens, and alpha-dystroglycanopathies caused by impaired synthesis of O-mannose glycans. Neither class of disorders are routinely picked up by CDG analysis in serum but are typically diagnosed using molecular methods (CDGGP / Congenital Disorders of Glycosylation Gene Panel, Varies).

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Ratio

Normal

Indeterminate

Abnormal

Transferrin mono-oligo/di-oligo ratio

< or =0.06

0.07-0.09

> or =0.10

Transferrin A-oligo/di-oligo ratio

< or =0.011

0.012-0.021

> or =0.022

Transferrin tri-sialo/di-oligo ratio

< or =0.05

0.06-0.12

> or =0.13

Apo CIII-1/Apo CIII-2 ratio

< or =2.91

2.92-3.68

> or =3.69

Apo CIII-0/Apo CIII-2 ratio

< or =0.48

0.49-0.68

> or =0.69

 

Interpretation
Provides information to assist in interpretation of the test results

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 show 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 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, the defects most likely 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 on 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 identify the correct form of CDG more precisely. If applicable, 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.

 

For more information, see Transferrin and Lipoprotein-CIII Isoform Analysis.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Lefeber DJ, Morava E, Jaeken J: How to find and diagnose a CDG due to defective N-glycosylation. J Inherit Metab Dis. 2011 Aug;34(4):849-852

2. Peanne R, de Lonlay P, Foulquier F, et al: Congenital disorders of glycosylation (CDG): Quo vadis? Eur J Med Genet. 2018 Nov;61(11):643-663

3. Freeze HH, Eklund EA, Ng BG, Patterson MC: Neurology of inherited glycosylation disorders. Lancet Neurol. 2012 May;11(5):453-466

4. Hennet T, Cabalzar J: Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction. Trends Biochem Sci. 2015 Jul;40(7):377-384

5. Freeze HH, Chong JX, Bamshad MJ, Ng BG: Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am J Hum Genet. 2014 Feb 6;94(2):161-175

6. 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 April 25, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1332/

7. Ng BG, Freeze HH: Human genetic disorders involving glycosylphosphatidylinositol (GPI) anchors and glycosphingolipids (GSL). J Inherit Metab Dis. 2015 Jan;38(1):171-178. doi:10.1007/s10545-014-9752-1

8. Bouchet-Seraphin C, Vuillaumier-Barrot S, Seta N. Dystroglycanopathies: About numerous genes involved in glycosylation of one single glycoprotein. J Neuromuscul Dis. 2015;2(1):27-38

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Serum is diluted with water and then subjected to online immunoaffinity chromatography coupled to a quadrupole time-of-flight mass spectrometer. Relative quantitation of carbohydrate deficient transferrin and apolipoprotein CIII is achieved by comparing glycoform ratios in each protein.(Unpublished Mayo method).

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Thursday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 6 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 month

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82373

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
CDG CDG, S 90417-7
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.
BG160 Reason for Referral 42349-1
31721 Mono-oligo/Di-oligo Ratio 35469-6
31720 A-oligo/Di-oligo Ratio 35475-3
50820 Interpretation 53808-2
50822 Reviewed By 18771-6
34474 Tri-sialo/Di-oligo Ratio 90420-1
34476 Apo CIII-1/Apo CIII-2 Ratio 90421-9
34475 Apo CIII-0/Apo CIII-2 Ratio 90419-3

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports