Glycan susceptibility factors in autism spectrum disorders

Abstract

Idiopathic autism spectrum disorders (ASDs) are neurodevelopmental disorders with unknown etiology. An estimated 1:68 children in the U.S. are diagnosed with ASDs, making these disorders a substantial public health issue. Recent advances in genome sequencing have identified numerous genetic variants across the ASD patient population. Many genetic variants identified occur in genes that encode glycosylated extracellular proteins (proteoglycans or glycoproteins) or enzymes involved in glycosylation (glycosyltransferases and sulfotransferases). It remains unknown whether “glycogene” variants cause changes in glycosylation and whether they contribute to the etiology and pathogenesis of ASDs. Insights into glycan susceptibility factors are provided by studies in the normal brain and congenital disorders of glycosylation, which are often accompanied by ASD-like behaviors. The purpose of this review is to present evidence that supports a contribution of extracellular glycans and glycoconjugates to the etiology and pathogenesis of idiopathic ASDs and other types of pervasive neurodevelopmental disorders.

Neurodevelopmental Changes in Excitatory Synaptic Structure and Function in the Cerebral Cortex of Sanfilippo Syndrome IIIA Mice

“…Further studies are warranted to explore the relationship of HS content and composition in synaptic biology not only in MPS disorders, but also in other neurodevelopmental and neurodegenerative disorders that have shared characteristics with MPS III32.…”

Proteoglycans in brain development and pathogenesis

“…PGs have been implemented in other neurodevelopmental disorders and neurodegenerative diseases that affect broader patient populations, and whose etiologies remain unknown. Autism spectrum disorders (affecting 1 in 70 children), and Alzheimer's (1 of 8 adults of 65 years old and over) and Parkinson's (1 in 1000 adults) diseases have all been linked to abnormal glycan variants, including PGs . For example, mutations in a unique dual‐function glycosyltransferase, encoded by the LARGE gene, that synthesizes repeating disaccharides of xylose and glucuronic acid and can modify dystroglycan (previously identified as CRANIN ), affect dystroglycan's capacity for binding to other ECM components and have been identified in cases of noncomplex autism .…”

Levels of Salivary Sialic Acid in Children with Autism Spectrum Disorder; Could It Be Related to Stereotypes and Hyperactivity?

“…Despite intense research efforts over the past decade, the etiology of idiopathic ASD is stil unknown whereas syndromic ASD is secondary to a primary condition caused by a single gene mutation, for example fragile X syndrome 2). Also, researchers suggested that the place alterations in developmental transcriptional regulation, brain growth, changes in the excitatory/inhibitory balance of the neural network, and abnormalities in neural plasticity might have a role in pathogenesis 3)…”