Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May;11(5):453-66.
doi: 10.1016/S1474-4422(12)70040-6.

Neurology of inherited glycosylation disorders

Hudson H Freeze  1 , Erik A Eklund, Bobby G Ng, Marc C Patterson
Affiliations

Neurology of inherited glycosylation disorders

Hudson H Freeze et al. Lancet Neurol. 2012 May.

Abstract

Congenital disorders of glycosylation comprise most of the nearly 70 genetic disorders known to be caused by impaired synthesis of glycoconjugates. The effects are expressed in most organ systems, and most involve the nervous system. Typical manifestations include structural abnormalities (eg, rapidly progressive cerebellar atrophy), myopathies (including congenital muscular dystrophies and limb-girdle dystrophies), strokes and stroke-like episodes, epileptic seizures, developmental delay, and demyelinating neuropathy. Patients can also have neurological symptoms associated with coagulopathies, immune dysfunction with or without infections, and cardiac, renal, or hepatic failure, which are common features of glycosylation disorders. The diagnosis of congenital disorder of glycosylation should be considered for any patient with multisystem disease and in those with more specific phenotypic features. Measurement of concentrations of selected glycoconjugates can be used to screen for many of these disorders, and molecular diagnosis is becoming more widely available in clinical practice. Disease-modifying treatments are available for only a few disorders, but all affected individuals benefit from early diagnosis and aggressive management.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

MCP acts as a consultant for Shire HGT and is Chair of the data monitoring committee for Stem Cells Inc. He has received travel expenses from the National Niemann-Pick Disease Foundation and the US Institute of Medicine (as a member of the Committee on Adverse Effects of Vaccines), and is a member of the WHO Topic Advisory Group (Neurology) – Revision of ICD-10, for which he receives no compensation or expenses. The other authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Pathways of glycosylation in the endoplasmic reticulum-Golgi network of mammalian cells
The main types of glycosylation are shown. Various representative sugar-chain structures are given as examples. The grey shaded areas denote common core regions. Most of the glycosylation disorders that affect the nervous system involve alterations in N-linked and O-mannosylated glycoproteins. Some glycophosphatidylinositol-anchor and glycosphingolipid disorders also involve these alterations, but most proteoglycan and O-GalNAc defects do not. Other types of glycosylation exist, such as cytoplasmic O-GlcNAc and C-mannosylation, but are not shown. Glc=glucose. Gal=galactose. Man=mannose. GlcNAc=N-acetylglucosamine. GalNAc=N-acetylgalactosamine. GlcA=glucuronic acid. IdoA=Iduronic acid. Fuc=fucose. Xyl=xylose. Sia=sialic acid. S=sulphation. P=phosphorylation. Ac=acetylation. S/T=serine or threonine. Adapted from Stanley and colleagues, by permission of the Consortium of Glycobiology Editors, La Jolla, CA, USA.
Figure 2
Figure 2. Clinical features of PMM2-CDG (CDG-1a)
Children frequently present with (A) facies and esotropia, (B) nipple inversion, and (C) supragluteal fat pads.
Figure 3
Figure 3. Cranial MRI in a patient with PMM2-CDG (CDG-1a)
Images were obtained from a girl aged 17 years. Notable atrophy of the cerebellar vermis and hemispheres can be seen in (A) sagittal T1, (B) axial T2, and (C) coronal fluid-attenuated inversion recovery images.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Freeze HH. Genetic defects in the human glycome. Nat Rev Genet. 2006;7:537–51. - PubMed
    1. Ungar D. Golgi linked protein glycosylation and associated diseases. Semin Cell Dev Biol. 2009;20:762–69. - PubMed
    1. Varki A. Biological roles of oligosaccharides: all of the theories are correct. Glycobiology. 1993;3:97–130. - PMC - PubMed
    1. Jaeken J, Hennet T, Freeze HH, Matthijs G. On the nomenclature of congenital disorders of glycosylation (CDG) J Inherit Metab Dis. 2008;31:669–72. - PubMed
    1. Stanley P, Schachter H, Taniguchi N. N-Glycans. In: Varki A, Cummings RD, Esko JD, et al., editors. Essentials of glycobiology. 2. New York, NY: Cold Spring Harbor Laboratory Press; 2009.

Publication types