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CSF N‐glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder

CSF N‐glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis... Protein N‐glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N‐glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late‐onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2‐ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co‐occurrence of psychiatric disturbances. We studied the N‐glycome profile of the cerebrospinal fluid (CSF) in a 14 year‐old patient with GM2‐gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work‐up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N‐glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo‐core fucosylated bisected N‐glycans. No changes of total plasma N‐glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N‐glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2‐gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. Autism Res 2016, 9: 423–428. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Autism Research Wiley

CSF N‐glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder

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References (29)

Publisher
Wiley
Copyright
© 2016 International Society for Autism Research, Wiley Periodicals, Inc.
ISSN
1939-3792
eISSN
1939-3806
DOI
10.1002/aur.1541
pmid
26286102
Publisher site
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Abstract

Protein N‐glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N‐glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late‐onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2‐ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co‐occurrence of psychiatric disturbances. We studied the N‐glycome profile of the cerebrospinal fluid (CSF) in a 14 year‐old patient with GM2‐gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work‐up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N‐glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo‐core fucosylated bisected N‐glycans. No changes of total plasma N‐glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N‐glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2‐gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. Autism Res 2016, 9: 423–428. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Journal

Autism Research – Wiley

Published: Apr 1, 2016

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