Final Congenital Disorders of Glycosylation-final...2021/01/04 · Aebi M, Hennet T. Congenital disorders of glycosylation: genetic model systems lead the way. Trends in Cell Biology.
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Glycosylation• Post-translational modification of proteins and lipids with sugars
(glycans)• Results in glycoconjugates• Complexity in assembly and processing of each glycoconjugate• Common eukaryotic types: proteoglycans, sphingolipids, GPI-
anchored, N- and O-linked• Categorized per the nature of the linkage to the protein or lipid• Mediate a wide variety of cellular metabolic processes• Increases the functional diversity of an organism
Reprinted from ScienceDirect, 34/6, Ng B and Freeze H, Perspectives on glycoslyation and its congenital disorders, 466-476., Copyright (2018), with permission from Elsevier.
defective glycosylation• Classified according to isoform
patterns in Tf analysis: CDG-type I, II, or mixed type
• Expanded criteria• Clinical features and severity are
variable• The majority are AR
Reprinted from ScienceDirect, 34/6, Ng B and Freeze H, Perspectives on glycoslyation and its congenital disorders, 466-476., Copyright (2018), with permission from Elsevier.
Biochemical Diagnostic Work-Up• Begin with serum transferrin and apolipoprotein-CIII isoform
simultaneous analysis by ESI-MS (MCL test: CDG)• Advantages:
• High throughput, fast, small sample volume• Detects abnormal N- and mucin-type core-1 O-glycosylation• Possible to detect abnormal glycans transferred onto Tf and Apo-CIII
• Disadvantages• Profile may be abnormal due to secondary causes• Rare cases have a normal Tf profile or can normalize over time
• Total serum N-glycan analysis (MCL test CDGN)• Free oligosaccharides analysis (MCL test OLIGU)
Mayo Clinic Experience• Two decades of performing CDG analysis• Average over 4,000/year since 2012• Different types of CDG patterns based on >300 confirmed
positive patient profiles• CLIR bioinformatic software to establish normal transferrin and
Apo-CIII reference ranges• Reference range established using >19,000 samples
2. Ng B, Freeze H. Perspectives on glycosylation and its congenital disorders. Trends in Genetics. 2018;34(6):466-476.
3. Aebi M, Hennet T. Congenital disorders of glycosylation: genetic model systems lead the way. Trends in Cell Biology. 2001;11(3):136-141.
4. Ajit Varki, Cummings RD, Esko JD, et al. Essentials of glycobiology.3rd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2015-2017. Accessed October 16, 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK310274/.
5. ALG1-congenital disorder of glycosylation: MedlinePlus Genetics. medlineplus.gov. Published December 1, 2017. Accessed October 8, 2020. https://medlineplus.gov/genetics/condition/alg1-congenital-disorder-of-glycosylation/.
6. Peanne R, de Lonlay P, Foulquier F, et al. Congenital disorders of glycosylation (CDG): Quo vadis? Eur J Med Genet. 2018;61(11):643–663.
7. Clinical and basic investigations into congenital disorders of flycosylation. Mayo Clinic. https://www.mayo.edu/research/clinical-trials/cls-20467386?_ga=2.149775990.1126976891.1596547642-1452676687.1548426765