Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder
Lysosomal free sialic acid storage disorder (FSASD) is a rare, multisystem disease caused by biallelic pathogenic variants in SLC17A5, encoding the lysosomal transmembrane sialic acid exporter, sialin. Defective sialin function leads to sialic acid accumulation in lysosomes, contributing to neurodeg...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950008725000092 |
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| author | Marya S. Sabir Lynne Wolfe David R. Adams Carla Ciccone Forbes D. Porter William A. Gahl Marjan Huizing Frances M. Platt May Christine V. Malicdan |
| author_facet | Marya S. Sabir Lynne Wolfe David R. Adams Carla Ciccone Forbes D. Porter William A. Gahl Marjan Huizing Frances M. Platt May Christine V. Malicdan |
| author_sort | Marya S. Sabir |
| collection | DOAJ |
| description | Lysosomal free sialic acid storage disorder (FSASD) is a rare, multisystem disease caused by biallelic pathogenic variants in SLC17A5, encoding the lysosomal transmembrane sialic acid exporter, sialin. Defective sialin function leads to sialic acid accumulation in lysosomes, contributing to neurodegeneration. While glycosphingolipid (GSL) metabolism is altered in other lysosomal storage disorders, its role in FSASD remains poorly understood, especially due to the restricted availability of biospecimens. This study investigated GSL levels in FSASD plasma and cerebrospinal fluid (CSF) using two normal-phase high-performance liquid chromatography assays. In plasma, GM1a was significantly elevated, while GM2 was decreased, with no significant alterations in other GSL species. In CSF, total GSLs, GM1a, GM3, GD3, GD1a, and GD1b were significantly elevated compared to comparison samples. These results reveal dysregulated GSL metabolism and suggest the potential of gangliosides as biomarkers. Further research is warranted to elucidate the biological implications of these alterations and their contributions to FSASD pathogenesis. |
| format | Article |
| id | doaj-art-a016c4307cee4966b80b1e62d67384be |
| institution | Kabale University |
| issn | 2950-0087 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Rare |
| spelling | doaj-art-a016c4307cee4966b80b1e62d67384be2025-02-02T05:29:39ZengElsevierRare2950-00872025-01-013100065Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage DisorderMarya S. Sabir0Lynne Wolfe1David R. Adams2Carla Ciccone3Forbes D. Porter4William A. Gahl5Marjan Huizing6Frances M. Platt7May Christine V. Malicdan8NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; NIH Oxford-Cambridge Scholars Program, University of Oxford, Oxford, United KingdomNIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USANIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USAHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USASection on Molecular Dysmorphology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USANIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USAHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USADepartment of Pharmacology, University of Oxford, Oxford, UK; Corresponding author.NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Corresponding author at: NIH Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.Lysosomal free sialic acid storage disorder (FSASD) is a rare, multisystem disease caused by biallelic pathogenic variants in SLC17A5, encoding the lysosomal transmembrane sialic acid exporter, sialin. Defective sialin function leads to sialic acid accumulation in lysosomes, contributing to neurodegeneration. While glycosphingolipid (GSL) metabolism is altered in other lysosomal storage disorders, its role in FSASD remains poorly understood, especially due to the restricted availability of biospecimens. This study investigated GSL levels in FSASD plasma and cerebrospinal fluid (CSF) using two normal-phase high-performance liquid chromatography assays. In plasma, GM1a was significantly elevated, while GM2 was decreased, with no significant alterations in other GSL species. In CSF, total GSLs, GM1a, GM3, GD3, GD1a, and GD1b were significantly elevated compared to comparison samples. These results reveal dysregulated GSL metabolism and suggest the potential of gangliosides as biomarkers. Further research is warranted to elucidate the biological implications of these alterations and their contributions to FSASD pathogenesis.http://www.sciencedirect.com/science/article/pii/S2950008725000092Salla diseaseSialinLipid metabolismGlycosphingolipidsGangliosidesLeukodystrophy |
| spellingShingle | Marya S. Sabir Lynne Wolfe David R. Adams Carla Ciccone Forbes D. Porter William A. Gahl Marjan Huizing Frances M. Platt May Christine V. Malicdan Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder Rare Salla disease Sialin Lipid metabolism Glycosphingolipids Gangliosides Leukodystrophy |
| title | Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder |
| title_full | Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder |
| title_fullStr | Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder |
| title_full_unstemmed | Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder |
| title_short | Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder |
| title_sort | changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with lysosomal free sialic acid storage disorder |
| topic | Salla disease Sialin Lipid metabolism Glycosphingolipids Gangliosides Leukodystrophy |
| url | http://www.sciencedirect.com/science/article/pii/S2950008725000092 |
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