Rodrigo Tzovenos Starosta , Angela J. Lee , Elizabeth R. Toolan , Miao He , Parith Wongkittichote , Earnest James Paul Daniel , Silvia Radenkovic , Rohit Budhraja , Akhilesh Pandey , Jaiprakash Sharma , Eva Morava , Hoanh Nguyen , Patricia I. Dickson
{"title":"D-甘露糖作为治疗褐藻糖激酶缺乏症相关先天性糖基化紊乱(FCSK-CDG)的一种新疗法","authors":"Rodrigo Tzovenos Starosta , Angela J. Lee , Elizabeth R. Toolan , Miao He , Parith Wongkittichote , Earnest James Paul Daniel , Silvia Radenkovic , Rohit Budhraja , Akhilesh Pandey , Jaiprakash Sharma , Eva Morava , Hoanh Nguyen , Patricia I. Dickson","doi":"10.1016/j.ymgme.2024.108488","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>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.</p></div><div><h3>Patient and methods</h3><p>In a so far unreported FCSK-CDG patient, we studied proteomics and glycoproteomics <em>in vitro</em> in patient-derived fibroblasts and also performed <em>in vivo</em> glycomics, before and after treatment with either D-Mannose or L-Fucose.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>D-mannose is a promising new treatment for FCSK-CDG.</p></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"142 2","pages":"Article 108488"},"PeriodicalIF":3.7000,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG)\",\"authors\":\"Rodrigo Tzovenos Starosta , Angela J. Lee , Elizabeth R. Toolan , Miao He , Parith Wongkittichote , Earnest James Paul Daniel , Silvia Radenkovic , Rohit Budhraja , Akhilesh Pandey , Jaiprakash Sharma , Eva Morava , Hoanh Nguyen , Patricia I. Dickson\",\"doi\":\"10.1016/j.ymgme.2024.108488\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>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.</p></div><div><h3>Patient and methods</h3><p>In a so far unreported FCSK-CDG patient, we studied proteomics and glycoproteomics <em>in vitro</em> in patient-derived fibroblasts and also performed <em>in vivo</em> glycomics, before and after treatment with either D-Mannose or L-Fucose.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>D-mannose is a promising new treatment for FCSK-CDG.</p></div>\",\"PeriodicalId\":18937,\"journal\":{\"name\":\"Molecular genetics and metabolism\",\"volume\":\"142 2\",\"pages\":\"Article 108488\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular genetics and metabolism\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S109671922400372X\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular genetics and metabolism","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S109671922400372X","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG)
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.
期刊介绍:
Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.