D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG)
Issued Date
2024-06-01
Resource Type
ISSN
10967192
eISSN
10967206
Scopus ID
2-s2.0-85192751629
Journal Title
Molecular Genetics and Metabolism
Volume
142
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Genetics and Metabolism Vol.142 No.2 (2024)
Suggested Citation
Starosta R.T., Lee A.J., Toolan E.R., He M., Wongkittichote P., Daniel E.J.P., Radenkovic S., Budhraja R., Pandey A., Sharma J., Morava E., Nguyen H., Dickson P.I. D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG). Molecular Genetics and Metabolism Vol.142 No.2 (2024). doi:10.1016/j.ymgme.2024.108488 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98374
Title
D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG)
Corresponding Author(s)
Other Contributor(s)
Abstract
Introduction: Fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG) is a rare autosomal recessive inborn error of metabolism characterized by a decreased flux through the salvage pathway of GDP-fucose biosynthesis due to a block in the recycling of L-fucose that exits the lysosome. FCSK-CDG has been described in 5 individuals to date in the medical literature, with a phenotype comprising global developmental delays/intellectual disability, hypotonia, abnormal myelination, posterior ocular disease, growth and feeding failure, immune deficiency, and chronic diarrhea, without clear therapeutic recommendations. Patient and methods: In a so far unreported FCSK-CDG patient, we studied proteomics and glycoproteomics in vitro in patient-derived fibroblasts and also performed in vivo glycomics, before and after treatment with either D-Mannose or L-Fucose. Results: We observed a marked increase in fucosylation after D-mannose supplementation in fibroblasts compared to treatment with L-Fucose. The patient was then treated with D-mannose at 850 mg/kg/d, with resolution of the chronic diarrhea, resolution of oral aversion, improved weight gain, and observed developmental gains. Serum N-glycan profiles showed an improvement in the abundance of fucosylated glycans after treatment. No treatment-attributed adverse effects were observed. Conclusion: D-mannose is a promising new treatment for FCSK-CDG.