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.Mahidol University2024-05-202024-05-202024-06-01Molecular Genetics and Metabolism Vol.142 No.2 (2024)10967192https://repository.li.mahidol.ac.th/handle/20.500.14594/98374Introduction: 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.Biochemistry, Genetics and Molecular BiologyMedicineReviewSCOPUS10.1016/j.ymgme.2024.1084882-s2.0-8519275162910967206