Neurological Aspects of Human Glycosylation Disorders

• Published in: Annual review of neuroscience Vol. 38; no. 1; pp. 105 - 125
• Main Authors: Freeze, Hudson H, Eklund, Erik A, Ng, Bobby G, Patterson, Marc C
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 08.07.2015; Annual Reviews, Inc
• Subjects: Animals; Autistic Disorder - complications; Autistic Disorder - metabolism; Basic Medicine; Biomarkers - metabolism; CDG; Cell adhesion & migration; congenital disorders; Congenital Disorders of Glycosylation - complications; Congenital Disorders of Glycosylation - metabolism; epilepsy; Epilepsy - complications; Epilepsy - metabolism; Eye Diseases - complications; Eye Diseases - metabolism; Genetic disorders; glycans; glycoprotein; Glycosaminoglycans - metabolism; Glycosylation; Humans; Intellectual Disability - complications; Intellectual Disability - metabolism; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Molecules; Nervous system; Neurosciences; Neurovetenskaper; Polysaccharides - metabolism; Proteins; seizures; epilepsy; seizures; glycoprotein; congenital disorders; glycans; CDG
• ISSN: 0147-006X; 1545-4126
• DOI: 10.1146/annurev-neuro-071714-034019

This review presents principles of glycosylation, describes the relevant glycosylation pathways and their related disorders, and highlights some of the neurological aspects and issues that continue to challenge researchers. More than 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and or peripheral nervous systems. Patients typically have developmental delays intellectual disabilities, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Among these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of misglycosylated products, which afflict a myriad of processes, including cell signaling, cell-cell interaction, and cell migration. This vast complexity in glycan composition and function, along with the limited availability of analytic tools, has impeded the identification of key glycosylated molecules that cause pathologies. To date, few critical target proteins have been pinpointed.