Neurology of inherited glycosylation disorders
TLDR
The diagnosis of congenital disorder of glycosylation should be considered for any patient with multisystem disease and in those with more specific phenotypic features, and molecular diagnosis is becoming more widely available in clinical practice.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.read more
Citations
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Journal ArticleDOI
Emerging Principles for the Therapeutic Exploitation of Glycosylation
TL;DR: The current knowledge of glycans in pathogen invasion, cancer, autoimmunity, and congenital diseases is reviewed and glycan engineering will continue to deliver enhanced therapeutic glycoproteins, such as antibodies, with enhanced disease modifying properties.
Journal ArticleDOI
Solving glycosylation disorders: fundamental approaches reveal complicated pathways.
TL;DR: It is predicted that some glycosylation disorders might occur with greater frequency than current estimates of their prevalence, and the prevalence of some disorders differs substantially between European and African Americans.
Journal ArticleDOI
Understanding human glycosylation disorders: biochemistry leads the charge.
TL;DR: Advances in genetics, especially next generation sequencing, propelled discovery of many glycosylation disorders in single and multiple pathways, suggesting novel perspectives for textbook biochemistry and novel research opportunities.
Journal ArticleDOI
Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway
Gregory M. Enns,Vandana Shashi,Matthew N. Bainbridge,Michael J. Gambello,Farah R. Zahir,Thomas Bast,Rebecca Crimian,Kelly Schoch,Julia Platt,Rachel Cox,Jonathan A. Bernstein,Mena Scavina,Rhonda S. Walter,Audrey L. Bibb,Melanie A. Jones,Madhuri Hegde,Brett H. Graham,Anna C. Need,Angelica Oviedo,Christian P. Schaaf,Christian P. Schaaf,Sean Michael Boyle,Atul J. Butte,Rong Chen,Michael J. Clark,Rajini R Haraksingh,Tina M. Cowan,Ping He,Sylvie Langlois,Huda Y. Zoghbi,Huda Y. Zoghbi,Michael Snyder,Richard A. Gibbs,Hudson H. Freeze,David Goldstein +34 more
TL;DR: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum–associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease.
Journal ArticleDOI
Neurological aspects of human glycosylation disorders.
TL;DR: The principles of glycosylation are presented, the relevant glyCosylation pathways and their related disorders are described, and some of the neurological aspects and issues that continue to challenge researchers are highlighted.
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