A spoonful of L-fucose

• Verfasst von: Feichtinger, René [VerfasserIn]
• Verfasst von: Hüllen, Andreas [VerfasserIn]
• Verfasst von: Koller, Andreas [VerfasserIn]
• Verfasst von: Kotzot, Dieter [VerfasserIn]
• Verfasst von: Grote, Valerian [VerfasserIn]
• Verfasst von: Rapp, Erdmann [VerfasserIn]
• Verfasst von: Hofbauer, Peter [VerfasserIn]
• Verfasst von: Brugger, Karin [VerfasserIn]
• Verfasst von: Thiel, Christian [VerfasserIn]
• Verfasst von: Mayr, Johannes A. [VerfasserIn]
• Verfasst von: Wortmann, Saskia B. [VerfasserIn]
• Titel: A spoonful of L-fucose
• Titelzusatz: an efficient therapy for GFUS-CDG, a new glycosylation disorder
• Verf.angabe: René G. Feichtinger, Andreas Hüllen, Andreas Koller, Dieter Kotzot, Valerian Grote, Erdmann Rapp, Peter Hofbauer, Karin Brugger, Christian Thiel, Johannes A. Mayr & Saskia B. Wortmann
• E-Jahr: 2021
• Jahr: 1 September 2021
• Umfang: 15 S.
• Fussnoten: Gesehen am 07.10.2021
• Titel Quelle: Enthalten in: European Molecular Biology OrganizationEMBO molecular medicine
• Ort Quelle: [London] : Nature Publishing Group UK, 2009
• Jahr Quelle: 2021
• Band/Heft Quelle: 13(2021), 9 vom: Sept., Artikel-ID e14332, Seite 1-15
• ISSN Quelle: 1757-4684
• DOI: doi:10.15252/emmm.202114332
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: congenital disorder of glycosylation
• Sach-SW: fucosylation
• Sach-SW: GDP-L-fucose synthase
• Sach-SW: salvage pathway
• Sach-SW: therapy
• K10plus-PPN: 1772733709

Abstract

Congenital disorders of glycosylation are a genetically and phenotypically heterogeneous family of diseases affecting the co- and posttranslational modification of proteins. Using exome sequencing, we detected biallelic variants in GFUS (NM_003313.4) c.[632G>A];[659C>T] (p.[Gly211Glu];[Ser220Leu]) in a patient presenting with global developmental delay, mild coarse facial features and faltering growth. GFUS encodes GDP-L-fucose synthase, the terminal enzyme in de novo synthesis of GDP-L-fucose, required for fucosylation of N- and O-glycans. We found reduced GFUS protein and decreased GDP-L-fucose levels leading to a general hypofucosylation determined in patient's glycoproteins in serum, leukocytes, thrombocytes and fibroblasts. Complementation of patient fibroblasts with wild-type GFUS cDNA restored fucosylation. Making use of the GDP-L-fucose salvage pathway, oral fucose supplementation normalized fucosylation of proteins within 4 weeks as measured in serum and leukocytes. During the follow-up of 19 months, a moderate improvement of growth was seen, as well as a clear improvement of cognitive skills as measured by the Kaufmann ABC and the Nijmegen Pediatric CDG Rating Scale. In conclusion, GFUS-CDG is a new glycosylation disorder for which oral L-fucose supplementation is promising.