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Open Access 01-01-2015 | Complex Lipids

Genetic defects in dolichol metabolism

Authors: Anna Buczkowska, Ewa Swiezewska, Dirk J. Lefeber

Published in: Journal of Inherited Metabolic Disease | Issue 1/2015

Abstract

Congenital disorders of glycosylation (CDG) comprise a group of inborn errors of metabolism with abnormal glycosylation of proteins and lipids. Patients with defective protein N-glycosylation are identified in routine metabolic screening via analysis of serum transferrin glycosylation. Defects in the assembly of the dolichol linked Glc₃Man₉GlcNAc₂ glycan and its transfer to proteins lead to the (partial) absence of complete glycans on proteins. These defects are called CDG-I and are located in the endoplasmic reticulum (ER) or cytoplasm. Defects in the subsequent processing of protein bound glycans result in the presence of truncated glycans on proteins. These defects are called CDG-II and the enzymes involved are located mainly in the Golgi apparatus. In recent years, human defects have been identified in dolichol biosynthesis genes within the group of CDG-I patients. This has increased interest in dolichol metabolism, has resulted in specific recognizable clinical symptoms in CDG-I and has offered new mechanistic insights in dolichol biosynthesis. We here review its biosynthetic pathways, the clinical and biochemical phenotypes in dolichol-related CDG defects, up to the formation of dolichyl-P-mannose (Dol-P-Man), and discuss existing evidence of regulatory networks in dolichol metabolism to provide an outlook on therapeutic strategies.

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Title: Genetic defects in dolichol metabolism
Authors: Anna Buczkowska
Ewa Swiezewska
Dirk J. Lefeber
Publication date: 01-01-2015
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 1/2015
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-014-9760-1

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