Genetic defects in dolichol metabolism
Publication year
2015Source
Journal of Inherited Metabolic Disease, 38, 1, (2015), pp. 157-69ISSN
Publication type
Article / Letter to editor
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Organization
Neurology
Laboratory Medicine
Journal title
Journal of Inherited Metabolic Disease
Volume
vol. 38
Issue
iss. 1
Page start
p. 157
Page end
p. 69
Subject
Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical NeuroscienceAbstract
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 Glc(3)Man(9)GlcNAc(2) 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.
This item appears in the following Collection(s)
- Academic publications [243859]
- Electronic publications [130603]
- Faculty of Medical Sciences [92795]
- Open Access publications [104912]
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