Publications
The STAR Foundation and our family community are extremely grateful to the scientists and clinicians working to learn more about FSASD/Salla.
Many publications listed below are open access to the public; however, please email us if there is a paywall and you would like to receive a copy for your personal use.
If you are a clinician or researcher interested in joining the Free Sialic Acid Disorders Consortium, please contact Dr Sarah Goebel.
Highlights
2023
Free Sialic Acid Storage Disease
Each chapter in GeneReviews is written by one or more experts on the specific condition or disease and goes through a rigorous editing and peer review process before being published online. STAR Foundation thanks FSASD Consortium experts Dr D. Adams, Dr M. Huizing and Dr M. Wasserstein for providing the 2025 update.
2021
Free sialic acid storage disorder: Progress and promise
FSASD is a rare genetic disease, causing sialic acid buildup that leads to developmental and movement problems. While no treatments exist yet, research is actively underway with support from experts and the STAR Foundation.
Recent publications
2025
Sabir, M. S., Dobrenis, K., Rha, A. K., Pollard, L., Leoyklang, P., Marrero, M., ... & Malicdan, M. C. V. Profiling glycosphingolipid changes in mouse and human cellular models of lysosomal free sialic acid storage disorder. Molecular Genetics and Metabolism Reports, 45, 101275.
In lab models of Lysosomal Free Sialic Acid Storage Disorder (FSASD), when the normal transporter for sialic acid is broken, the cells end up with too much free sialic acid — and this disrupts the balance of important fat sugar molecules (gangliosides), which could help explain how the disease causes damage.
2025
Sabir, M. S., Huizing, M., Gahl, W. A., Platt, F. M., & Malicdan, M. C. V. Dissecting the impact of N-acetylmannosamine (ManNAc) on ganglioside levels in a sialin-deficient cell model. Micropublication Biology, 2025, 10-17912.
People with a faulty “sialin” protein (as in FSASD) still cannot fully fix the abnormal processing of certain brain-related fats even when given extra building blocks. Supplying a precursor of sialic acid (N acetylmannosamine, ManNAc) is not enough to restore normal fat chemistry.
2025
Adams, D., Huizing, M., & Wasserstein, M. Free Sialic Acid Storage Disorder. GeneReviews® [Internet].
FSASD is a rare genetic disease where a sugar called sialic acid builds up in cells, especially in the brain. FSASD is caused by SLC17A5 mutations that impair the sialin protein, leading to the sialic acid buildup in cells, and resulting in cellular damage.
2025
Sabir, M. S., Hossain, M. S., Pollard, L., Huizing, M., Gahl, W. A., Platt, F. M., & Malicdan, M. C. V. Lack of significant ganglioside changes in Slc17a5 heterozygous mice: Relevance to FSASD and Parkinson's disease. Biochemistry and Biophysics Reports, 42, 101979.
Studies suggest that while SLC17A5 mutations cause FSASD and were suspected to influence Parkinson’s risk, mouse research found no major brain lipid changes, indicating the variant likely does not contribute to Parkinson’s disease.
2025
Sabir, M. S., Makarious, M. B., Huizing, M., Gahl, W. A., Platt, F. M., & Malicdan, M. C. V. Comprehensive analysis of SLC17A5 variants in large European cohorts reveals no association with Parkinson's disease risk. Parkinsonism & Related Disorders, 134, 107790.
Parkinson’s disease has been linked to problems in lysosomes (the cell’s recycling centers). Researchers examined whether SLC17A5 gene changes, which cause FSASD, might increase Parkinson’s risk, but large European studies found no significant connection.
2025
Sabir, M. S., Pollard, L., Wolfe, L., Adams, D. R., Ciccone, C., Leoyklang, P., ... & Malicdan, M. C. V. Investigating the Utility of Leukocyte Sialic Acid Measurements in Lysosomal Free Sialic Acid Storage Disorder. JIMD reports, 66(4), e70029.
Measuring free sialic acid in white blood cells can reliably detect FSASD, offering a simpler and less invasive way to diagnose and monitor the disease.
2025
Sabir, M. S., Wolfe, L., Adams, D. R., Ciccone, C., Porter, F. D., Gahl, W. A.,… & Malicdan, M. C. V. Changes in glycosphingolipid levels in plasma and cerebrospinal fluid of individuals with Lysosomal Free Sialic Acid Storage Disorder. Rare, 3, 100065.
FSASD patients show abnormal levels of certain brain lipids (gangliosides) in blood and spinal fluid, which could help track the disease and guide future studies.
2025
Sabir, M.S., Jovanovic, V.M., Ryu, S. et al. Lysosomal free sialic acid storage disorder iPSC-derived neural cells display altered glycosphingolipid metabolism. Sci Rep 15, 29708
Scientists found that in FSASD, different brain cell types, especially astrocytes, show increased free sialic acid, altered enzymes, and other cellular changes, shedding light on how the disease damages the brain.
2024
Sabir, M. S., Leoyklang, P., Hackbarth, M. E., Pak, E., Dutra, A., Tait, R., ... & Malicdan, M. C. V. Generation and characterization of two iPSC lines derived from subjects with Free Sialic Acid Storage Disorder (FSASD). Stem cell research, 81, 103600.
Scientists created stem cell models from both mild and intermediate FSASD patients to better study the disease and develop future treatments.
2023
Hu, W., Chi, C., Song, K., & Zheng, H. The molecular mechanism of sialic acid transport mediated by Sialin. Science Advances, 9(3), eade8346.
Scientists mapped the 3D shape of sialin, the protein that moves sialic acid out of cells’ recycling centers. They found the critical spots where changes (mutations) can break the protein and cause disease.
2023
Huizing M, Sabir M, Wolfe L, Adams D. Lysosomal Free Sialic Acid Storage Disorders. NORD Rare Disease Database Updated 8/2/2023
As part of the (US) National Organization for Rare Disorders database, scientists provide a disease overview of Free sialic acid storage disorders (which include Salla disease).
2023
Harb, J. F., Christensen, C. L., Kan, S. H., Rha, A. K., Andrade-Heckman, P., Pollard, L., ... & Wang, R. Y. Base editing corrects the common Salla disease SLC17A5 c. 115C> T variant. Molecular Therapy Nucleic Acids, 34.
Using base editing, scientists successfully corrected the main FSASD-causing SLC17A5 mutation in patient and mouse cells, reducing harmful sugar buildup more effectively and safely than traditional CRISPR methods.
2023
Adams DR, Huizing M, Wasserstein MP Free Sialic Acid Storage Disease. Orphanet ORPHA834.
Each chapter in GeneReviews is written by one or more experts on the specific condition or disease and goes through a rigorous editing and peer review process before being published online. STAR Foundation thanks FSASD Consortium experts Dr D. Adams, Dr M. Huizing and Dr M. Wasserstein for providing the 2025 update.
2021
Huizing, M., Hackbarth, M. E., Adams, D. R., Wasserstein, M., Patterson, M. C., Walkley, S. U., Gahl, W. A., & FSASD Consortium. Free sialic acid storage disorder: Progress and promise. Neuroscience letters, 755, 135896
FSASD is a rare genetic disease, causing sialic acid buildup that leads to developmental and movement problems. While no treatments exist yet, research is actively underway with support from experts and the STAR Foundation.
2020
Dubois, L., Pietrancosta, N., Cabaye, A., Fanget, I., Debacker, C., Gilormini, P. A., ... & Anne, C. Amino acids bearing aromatic or heteroaromatic substituents as a new class of ligands for the lysosomal sialic acid transporter sialin. Journal of Medicinal Chemistry, 63(15), 8231-8249.
Scientists identified compounds that bind and help correct malfunctioning sialin, including the R39C mutant, pointing to potential therapies for FSASD.
2020
Huizing, M., & Gahl, W. A. Inherited disorders of lysosomal membrane transporters. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1862(12), 183336.
The paper reviews genetic diseases caused by faulty lysosomal transporters, focusing on SLC17A5/sialin disorders like FSASD, and explains how disrupted lysosomal export leads to cellular damage, comparing them with similar conditions.
Additional publications (clinical)
2023
Chapleau, Alexandra, et al. "Longitudinal Characterization of the Clinical Course of Intermediate-Severe Salla Disease." Pediatric Neurology 148: 133-137.
2019
Zielonka, Matthias, et al. "A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease—an ultra-orphan multisystemic lysosomal storage disorder." Genetics in Medicine 21.2: 347-352.
2017
Robak, Laurie A., et al. "Excessive burden of lysosomal storage disorder gene variants in Parkinson’s disease." Brain 140.12: 3191-3203.
2017
Barmherzig, Rebecca, et al. "A new patient with intermediate severe Salla disease with hypomyelination: a literature review for Salla disease." Pediatric Neurology 74: 87-91.
2015
Paavola, Liisa E., et al. "A 13-year follow-up of Finnish patients with Salla disease." Journal of Neurodevelopmental Disorders 7.1: 20.
2012
Renaud, Deborah L. "Lysosomal disorders associated with leukoencephalopathy." Seminars in neurology. Vol. 32. No. 01. Thieme Medical Publishers.
2012
Paavola, Liisa E., et al. "An unusual developmental profile of Salla disease in a patient with the SallaFIN mutation." Case Reports in Neurological Medicine 2012.1: 615721.
2009
Mochel, Fanny, et al. "Free sialic acid storage disease without sialuria." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 65.6: 753-757.
2009
Coker, Mahmut, et al. "Salla disease in Turkish children: severe and conventional type." The Turkish Journal of Pediatrics 51.6: 605-609.
2007
Helip-Wooley, Amanda, Robert Kleta, and William A. Gahl. "Lysosomal free sialic acid storage disorders: Salla disease and ISSD." Lysosomal Storage Disorders. Boston, MA: Springer US. 499-511.
2005
Strauss, Kevin A., et al. "Genome‐wide SNP arrays as a diagnostic tool: clinical description, genetic mapping, and molecular characterization of Salla disease in an Old Order Mennonite population." American journal of medical genetics Part A 138.3: 262-267.
2005
Biancheri, R., et al. "Homozygosity for the p. K136E mutation in the SLC17A5 gene as cause of an Italian severe Salla disease." Neurogenetics 6.4: 195-199.
2004
Landau, D., et al. "A novel mutation in the SLC17A5 gene causing both severe and mild phenotypes of free sialic acid storage disease in one inbred Bedouin kindred." Molecular genetics and metabolism 82.2: 167-172.
2004
Ishiwari, Kouhei, et al. "Clinical, biochemical, and cytochemical studies on a Japanese Salla disease case associated with a renal disorder." Journal of human genetics 49.12: 656-663.
2004
Alajoki, Liisa, et al. "Neurocognitive profiles in Salla disease." Developmental medicine and child neurology 46.12: 832-837.
2004
Kleta, Robert, et al. "Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity." Molecular genetics and metabolism 82.2: 137-143.
2003
Kleta, Robert, et al. "Biochemical and molecular analyses of infantile free sialic acid storage disease in North American children." American Journal of Medical Genetics Part A 120.1: 28-33.
2003
Parazzini, Cecilia, et al. "Infantile sialic acid storage disease: serial ultrasound and magnetic resonance imaging features." American journal of neuroradiology 24.3 : 398-400.
2003
Martin, Rick A., et al. "Sialic acid storage disease of the Salla phenotype in American monozygous twin female sibs." American Journal of Medical Genetics Part A 120.1: 23-27.
2003
Christensen, P. Sønderby, P-H. Kaad, and J. R. Øtergaard. "Two cases of Salla disease in Danish children." Acta Paediatrica 92.11.
2003
Linnankivi, Tarja, Tuula Lönnqvist, and Taina Autti. "A case of Salla disease with involvement of the cerebellar white matter." Neuroradiology 45.2: 107-109.
2002
Varho, Tarja T., et al. "Phenotypic spectrum of Salla disease, a free sialic acid storage disorder." Pediatric neurology 26.4: 267-273.
2002
Biancheri, R., et al. "An Italian severe Salla disease variant associated with a SLC17A5 mutation earlier described in infantile sialic acid storage disease." Clinical genetics 61.6: 443-447.
2000
Aula, Nina, et al. "The spectrum of SLC17A5-gene mutations resulting in free sialic acid–storage diseases indicates some genotype-phenotype correlation." The American Journal of Human Genetics 67.4: 832-840.
2000
Varho, Tarja, et al. "Central and peripheral nervous system dysfunction in the clinical variation of Salla disease." Neurology 55.1: 99-104.
1999
Lemyre, Emmanuelle, et al. "Clinical spectrum of infantile free sialic acid storage disease." American journal of medical genetics 82.5: 385-391.
1999
Verheijen, Frans W., et al. "A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases." Nature genetics 23.4: 462-465.
1999
Sonninen, Pirkko, et al. "Brain involvement in Salla disease." American journal of neuroradiology 20.3: 433-443.
1996
Nakano, Chizuko, et al. "A Japanese case of infantile sialic acid storage disease." Brain and Development 18.2: 153-156.
1995
Schleutker, Johanna, et al. "Lysosomal free sialic acid storage disorders with different phenotypic presentations--infantile-form sialic acid storage disease and Salla disease--represent allelic disorders on 6q14-15." American journal of human genetics 57.4: 893.
1994
Haataja, Leena, et al. "Phenotypic variation and magnetic resonance imaging (MRI) in Salla disease, a free sialic acid storage disorder." Neuropediatrics 25.05: 238-244.
1991
Mancini, Grazia MS, et al. "Sialic acid storage disorders: observations on clinical and biochemical variation." Developmental neuroscience 13.4-5: 327-330.
1985
Similä, Seppo, et al. "Finnish type of sialic acid storage disease with sialuria (Salla disease): the occurrence and diagnostic significance of cytoplasmic vacuoles in blood lymphocytes." Journal of mental deficiency research 29: 179-186.
1985
Baumkötter, J., et al. "N-Acetylneuraminic acid storage disease." Human genetics 71.2: 155-159.
1983
Renlund, Martin, et al. "Salla disease: a new lysosomal storage disorder with disturbed sialic acid metabolism." Neurology 33.1: 57-57.
1979
Aula, Pertti, et al. "'Salla disease: a new lysosomal storage disorder." Archives of Neurology 36.2: 88-94.
Additional publications (molecular/cellular)
2025
Sabir,Marya et al "Dissecting the impact of N-acetylmannosamine (ManNAc) on ganglioside levels in a sialin-deficient cell model"
2025
Wang, Jinsong, et al. "Nitrate ameliorates myelin loss and cognitive impairment in Alzheimer’s disease through upregulation of neuronal sialin and subsequent inhibition of TPPP phosphorylation."
2020
Dubois, Lilian, et al. "Amino acids bearing aromatic or heteroaromatic substituents as a new class of ligands for the lysosomal sialic acid transporter sialin." Journal of Medicinal Chemistry 63.15: 8231-8249.
2018
Pshezhetsky, Alexey V., and Mila Ashmarina. "Keeping it trim: roles of neuraminidases in CNS function." Glycoconjugate journal 35.4: 375-386.
2018
Gilormini, Pierre André, et al. "Chemical glycomics enrichment: imaging the recycling of sialic acid in living cells." Journal of inherited metabolic disease 41.3: 515-523.
2017
Stroobants, Stijn, et al. "Progressive leukoencephalopathy impairs neurobehavioral development in sialin-deficient mice." Experimental neurology 291: 106-119.
2015
Yoo, Seung-Wan, et al. "Sialylation regulates brain structure and function." The FASEB Journal 29.7: 3040.
2013
Morland, Cecilie, et al. "Vesicular uptake and exocytosis of L-aspartate is independent of sialin." The FASEB Journal 27.3: 1264.
2011
Miyaji, Takaaki, Hiroshi Omote, and Yoshinori Moriyama. "Functional characterization of vesicular excitatory amino acid transport by human sialin." Journal of neurochemistry 119.1: 1-5.
2010
Courville, Pascal, Matthias Quick, and Richard J. Reimer. "Structure-function studies of the SLC17 transporter sialin identify crucial residues and substrate-induced conformational changes." Journal of Biological Chemistry 285.25: 19316-19323.
2009
Ruivo, Raquel, et al. "Molecular and cellular basis of lysosomal transmembrane protein dysfunction." Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1793.4: 636-649.
2009
Prolo, Laura M., Hannes Vogel, and Richard J. Reimer. "The lysosomal sialic acid transporter sialin is required for normal CNS myelination." Journal of Neuroscience 29.49: 15355-15365.
2008
Miyaji, Takaaki, et al. "Identification of a vesicular aspartate transporter." Proceedings of the National Academy of Sciences 105.33: 11720-11724.
2008
Sagne, C., and B. Gasnier. "Molecular physiology and pathophysiology of lysosomal membrane transporters." Journal of inherited metabolic disease 31.2: 258-266.
2008
Kuskonmaz, Barıs, et al. "Lymphocytic vacuolization in sialic acid storage disease." American journal of hematology 83.10: 821-821.
2008
Ruivo, Raquel, et al. "Molecular pathogenesis of sialic acid storage diseases: insight gained from four missense mutations and a putative polymorphism of human sialin." Biology of the Cell 100.9: 551-559.
2007
Myall, Nathaniel J., et al. "G328E and G409E sialin missense mutations similarly impair transport activity, but differentially affect trafficking." Molecular genetics and metabolism 92.4: 371-374.
2005
Wreden, Christopher C., Marcin Wlizla, and Richard J. Reimer. "Varied Mechanisms Underlie the Free Sialic Acid Storage Disorders." Journal of Biological Chemistry 280.2: 1408-1416.
2004
Morin, Pierre, Corinne Sagné, and Bruno Gasnier. "Functional characterization of wild‐type and mutant human sialin." The EMBO journal 23.23: 4560-4570.
2004
Aula, Nina, et al. "Sialin expression in the CNS implicates extralysosomal function in neurons." Neurobiology of disease 15.2: 251-261.
2002
Aula, Nina, et al. "Unraveling the molecular pathogenesis of free sialic acid storage disorders: altered targeting of mutant sialin." Molecular genetics and metabolism 77.1-2: 99-107.
1996
Pitto, Marina, et al. "Impairment of ganglioside metabolism in cultured fibroblasts from Salla patients." Clinica chimica acta 247.1-2: 143-157.
1996
Chigorno, Vanna, Guido Tettamanti, and Sandro Sonnino. "Metabolic Processing of Gangliosides by Normal and Salla Human Fibroblasts in Culture: A STUDY PERFORMED BY ADMINISTERING RADIOACTIVE GM3 GANGLIOSIDE." Journal of Biological Chemistry 271.36: 21738-21744.
1991
Mancini, G. M., et al. "Sialic acid storage diseases. A multiple lysosomal transport defect for acidic monosaccharides." The Journal of clinical investigation 87.4: 1329-1335.
1990
Blom, H. J., et al. "Defective glucuronic acid transport from lysosomes of infantile free sialic acid storage disease fibroblasts." Biochemical Journal 268.3: 621-625.
1989
Mancini, G. M., et al. "Characterization of a proton-driven carrier for sialic acid in the lysosomal membrane: evidence for a group-specific transport system for acidic monosaccharides." Journal of Biological Chemistry 264.26: 15247-15254.
1989
Tietze, F., et al. "Defective lysosomal egress of free sialic acid (N-acetylneuraminic acid) in fibroblasts of patients with infantile free sialic acid storage disease." Journal of Biological Chemistry 264.26: 15316-15322.
1988
Mendla, K., et al. "Defective lysosomal release of glycoprotein-derived sialic acid in fibroblasts from patients with sialic acid storage disease." Biochemical Journal 250.1: 261-267.
1986
Renlund, Martin, Frank Tietze, and William A. Gahl. "Defective sialic acid egress from isolated fibroblast lysosomes of patients with Salla disease." Science 232.4751: 759-762.
1983
Renlund, Martin, et al. "Free N‐acetylneuraminic acid in tissues in Salla disease and the enzymes involved in its metabolism." European journal of biochemistry 130.1: 39-45.
