Last updated:
3/3/2026
Years published: 2010, 2013, 2016, 2019, 2023, 2026
NORD gratefully acknowledges Marjan Huizing, PhD, Marya Sabir, BS, Lynne Wolfe, MS, CRNP, BC, and David Adams, MD, PhD, Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, as well as Gabrielle Schuh and Meghan Werner, Genetic Counseling students from Emory University and Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for their assistance with the preparation of this report.
Summary
Free sialic acid storage disorder (FSASD) is a rare neurodegenerative, multisystem disorder characterized by abnormal accumulation of free sialic acid (a sugar molecule) in various tissues and organs of the body.
FSASD includes a range of conditions that vary in severity. In the past, doctors described three main forms along this spectrum:
All forms involve progressive neurological impairment, although severity and rate of progression vary.
FSASD is caused by disease causing changes (pathogenic variants) in the SLC17A5 gene. Inheritance is autosomal recessive, meaning an affected child inherits one pathogenic variant from each parent.
Currently, there is no cure or disease-specific treatment that can stop or reverse FSADS associated symptoms.
The signs and symptoms and severity of FSASD vary widely. Some people develop severe, life-threatening complications; others will have milder findings. The more severely affected patients usually exhibit symptoms within six months of birth or even before birth; milder cases may become apparent later during infancy or childhood. Affected individuals may not have all the symptoms discussed below, but all have some degree of degeneration of nerve cells (neurodegeneration) and developmental delay.
Severe FSASD
Symptoms of severe FSASD (also called infantile sialic acid storage disorder, ISSD) are usually apparent at birth or early in infancy; some infants may be born prematurely or die in the womb. Affected infants may have fluid accumulation in the body (hydrops fetalis) before or soon after birth and abnormal enlargement of the liver and spleen (hepatosplenomegaly). Other signs and symptoms may include:
Severe FSASD eventually progresses to cause life-threatening complications such as serious respiratory infections and abnormal enlargement of the heart (cardiomegaly). Some infants develop nephrotic syndrome, in which damage to the kidneys causes them to leak large quantities of protein into the urine (proteinuria). Nephrotic syndrome can cause swelling in the arms and legs, around the eyes, or in other areas due to fluid accumulation (edema). Additional symptoms may include a swollen abdomen, unintended weight gain, and high blood pressure.
Most affected children die in infancy or early childhood, although survival can vary.
Mild FSASD
Mild FSASD (also called Salla disease) is the least severe form of the disorder and has an increased population frequency in Finland. The specific symptoms and severity can vary from one individual to another. Although Salla disease can cause life-threatening complications, some individuals have lived into their 70s. Affected infants appear normal at birth, but symptoms become apparent during the first year of life. Such symptoms include:
Approximately two-thirds of children with mild FSASD eventually learn to walk. Some degree of speech impairment is usually present. Affected infants may learn single words or small sentences, but this ability may be lost as they age. The ability to speak is affected more severely than the ability to understand speech. Affected children exhibit some degree of cognitive impairment as well.
Some people with mild FSASD may not develop symptoms until later in childhood when a variety of neurological findings become apparent. These include seizures, involuntary muscle spasms that result in slow, stiff movements of the legs (spasticity), and repetitive, involuntary, writhing movements of the arms and legs (athetosis). Some individuals who previously developed the ability to walk or talk may lose these skills (regression). Some individuals may experience a gradual coarsening of facial features.
Intermediate FSASD
The severity of intermediate FSASD can vary greatly from one individual to another. Only a handful of people with intermediate lysosomal free sialic acid storage disease have been reported in medical literature; much about the subtype remains unclear. The symptoms are similar to those of the mild and severe forms of the disease, but less severe than severe FSASD and more severe than mild FSASD. The first symptoms begin within the first six months of life and include hypotonia (low muscle tone) and developmental delay. Dystonia (sharp, repetitive muscle movements) was also reported among the few reported cases, though the timing of onset is unclear.
FSASD is caused by changes (variants) in the SLC17A5 gene. The SLC17A5 gene contains instructions for producing (encoding) a protein called sialin that is required to transport free sialic acid out of lysosomes and into the cytosol of cells. Sialic acid is a charged sugar produced when lysosomes break down certain sugar-containing proteins (glycoproteins), carbohydrates or fats (glycolipids). In sialic acid storage disorders, deficient levels of functioning sialin result in the accumulation (storage) of free sialic acid in lysosomes.
FSASD is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a changed gene from each parent. If an individual receives one normal gene and one changed gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the changed gene and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
FSASD is very rare. Worldwide, it is estimated to affect about 1 to 3 people per 1 million. The condition is more common in Finland, where about 35 per 1 million people are affected. This is due to a specific genetic change in the SLC17A5 gene, called the p.Arg39Cys founder variant, which is more common in people of Finnish ancestry.
About 260 individuals worldwide have been reported to have FSASD confirmed by genetic testing, with another 50 described based on clinical features alone. Among those with a confirmed diagnosis, about 80% carry the p.Arg39Cys variant.
FSASD has been identified in diverse populations worldwide and it affects males and females in equal numbers. Individuals with FSASD may go misdiagnosed or undiagnosed, making it difficult to determine the true frequency of the disease in the general population.
A diagnosis of a FSASD may be suspected based upon identification of characteristic signs and symptoms and by performing a thorough clinical evaluation, a detailed patient history (including family history) and specialized tests that detect elevated levels of free sialic acid in certain cells and tissues or in urine.
A suspected diagnosis before birth (prenatally) is possible through chorionic villus sampling (CVS). During CVS, fetal tissue samples are removed, and tests (assays) are performed on cultured tissue cells and/or white blood cells (leukocytes) to detect elevated levels of free sialic acid.
The diagnosis of FSASD is ultimately confirmed by identifying disease-causing genetic variant(s) in the SLC17A5 gene by molecular genetic testing. This testing is available on a clinical basis.
Treatment
There is no disease-modifying treatment specific for FSASD. Treatment is directed toward the specific symptoms that are apparent in each individual. Seizures are treated by generally accepted standards including the use of anticonvulsants.
Early intervention is important in ensuring that children with FSASD reach their highest potential. Services that may be beneficial include special education, physical therapy to improve strength and coordination, speech therapy and other medical, social, and/or vocational services.
Genetic counseling is recommended for affected individuals and their families.
Collaborative research efforts involving academic investigators, the National Institutes of Health (USA), and the Salla Treatment and Research (S.T.A.R.) Foundation aim to address the scientific, clinical, and funding challenges involved in developing new therapies.
Investigational approaches under study include gene therapy strategies designed to restore SLC17A5 gene function. While enzyme replacement therapy is used in some other lysosomal storage disorders, it is not currently an established treatment approach for FSASD.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Huizing M, Hackbarth ME, Adams DR, Wasserstein M, Patterson MC, Walkley SU, Gahl WA; FSASD Consortium. Free sialic acid storage disorder: Progress and promise. Neurosci Lett. 2021;755:135896. DOI: 10.1016/j.neulet.2021.135896
Zielonka M, Garbade SF, Kölker S, Hoffmann GF, Ries M. A cross-sectional quantitative analysis of the natural history of free sialic acid storage disease-an ultra-orphan multisystemic lysosomal storage disorder. Genet Med. 2019;21(2):347-352. DOI: 10.1038/s41436-018-0051-3
Barmherzig R, Bullivant G, Cordeiro D, Sinasac DS, Blaser S, Mercimek-Mahmutoglu S. A new patient with intermediate severe Salla disease with hypomyelination: a literature review for Salla disease. Pediatr Neurol. 2017;74:87-91.e2. DOI: 10.1016/j.pediatrneurol.2017.05.022
Paavola LE, Remes AM, Harila MJ, Varho TT, Korhonen TT, Majamaa K. A 13-year follow-up of Finnish patients with Salla disease. J Neurodev Disord. 2015;7(1):20. DOI: 10.1186/s11689-015-9116-7
Alajoki L, Varho T, Posti K, Aula P, Korhonen T. Neurocognitive profiles in Salla disease. Dev Med Child Neurol. 2004;46:832-837. DOI: 10.1017/s0012162204001458
Aula N, Aula P. Prenatal diagnosis of free sialic acid storage disorders (SASD). Prenat Diagn. 2006;26:655-658. DOI: 10.1002/pd.1431
Morse RP, Kleta R, Alroy J, Gahl WA. Novel form of intermediate salla disease: clinical and neuroimaging features. J Child Neurol. 2005;20:814-816. DOI: 10.1177/08830738050200100601
Wrenden CC, Wlizla M, Reimer RJ. Varied mechanisms underlie the free sialic acid storage disorders. J Biol Chem. 2005;280:1408-1416. DOI: 10.1074/jbc.M411295200
Kleta R, Aughton DJ, Rivkin MJ, et al. Biochemical and molecular analyses of infantile free sialic acid storage disease in North American children. Am J Med Genet A. 2003;120A:28-33. DOI: 10.1002/ajmg.a.20024
Aula N, Salomaki P, Timonen R, et al. Sialin expression in free sialic acid-storage diseases indicates some genotype-phenotype correlation. Am J Hum Genet. 2000;67:832-840. DOI: 10.1086/303077
Verheijen FW, Verbeek E, Aula N, Beerens CEMT, Havelaar AC, Joosse M, Peltonen L, Aula P, Galjaard H, van der Spek PJ, Mancini GM. A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases. Nat Genet. 1999; 23:462. DOI: 10.1038/70585
INTERNET
Adams D, Huizing M, Wasserstein M. Free Sialic Acid Storage Disorder. 2003 Jun 13 [Updated 2025 Jun 26]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1470/ Accessed on March 2, 2026.
Sialic acid storage disorder, infantile. Available at: https://omim.org/entry/269920?search=issd&highlight=issd Accessed on March 2, 2026.
Aula P, Gahl WA. Disorders of Free Sialic Acid Storage. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw Hill; 2019. Accessed November 30, 2022. https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225891389 Accessed on March 2, 2026.
Salla Disease. Online Mendelian Inheritance in Man (OMIM). Last Update 01/02/2014. Available at: https://omim.org/entry/604369 Accessed on March 2, 2026.
Sabir MS. SciBites 2022. Free Sialic Acid Storage Disorder. https://www.youtube.com/watch?v=_KGLD_UK0og Accessed on March 2, 2026.
Sabir MS. Three Minute Talks (TmT) NIH IRP 2022. Free Sialic Acid Storage Disorder. https://www.youtube.com/watch?v=PU_ektiuSQY Accessed on March 2, 2026.
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