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MPS IIIA is a rare lysosomal storage disorder that leads to toxic accumulation of heparan sulfate1,2

Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome type A) is a lysosomal storage disorder caused by a deficiency in the enzyme sulfamidase due to pathogenic variants of the SGSH gene.1,3,4

This deficiency leads to the toxic accumulation of heparan sulfate, resulting in cellular dysfunction and the clinical symptoms of MPS IIIA.1,5 The disease progression can vary from slow to rapid, depending on the specific genetic variants of the SGSH gene.1

Understanding where MPS IIIA fits in the classification of lysosomal storage disorders

Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome type A) is a lysosomal storage disorder caused by a deficiency in the enzyme sulfamidase due to a pathogenic variant of the SGSH gene.1,3,4

This deficiency leads to the toxic accumulation of heparan sulfate, resulting in cellular dysfunction and the clinical symptoms of MPS IIIA.1,5 The disease progression can vary from slow to rapid, depending on the specific genetic variant of the SGSH gene.1

Pathophysiology of MPS IIIA1,5

UNAFFECTED Form of SGSH
  • The unaffected form of SGSH carries instructions for cells to create sufficient sulfamidase
  • Sulfamidase metabolizes heparan sulfate
Variant Form of SGSH
  • The variant form of SGSH in children with MPS IIIA leads to an absent or dysfunctional sulfamidase
  • Deficiency in functional sulfamidase leads to toxic accumulation of heparan sulfate within cells, causing eventual cell damage
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Sulfamidase

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Heparan sulfate

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Dysfunctional sulfamidase

Parent carriers icon

MPS IIIA is an autosomal recessive disease caused by pathogenic variants of the SGSH gene.1

If both parents are carriers of pathogenic variants of the SGSH gene, there is a 1 in 4 chance with each pregnancy that they will have a child affected with MPS IIIA.1

Global prevalence icon

Estimated global prevalence:
Up to 1.62/100,000 live births6,7

United States prevalence icon

Prevalence in the United States:
~0.19/100,000 live births8

Learn about clinical presentation

Abbreviations: MPS, mucopolysaccharidosis; MPS IIIA, mucopolysaccharidosis type IIIA.

References

  1. Wagner VF, Northrup H. Mucopolysaccharidosis type III. 2019. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Accessed January 2, 2025. https://www.ncbi.nlm.nih.gov/books/NBK546574/
  2. Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: a mini-review. J Inherit Metab Dis. 2008;31(2):240-252.
  3. National Institutes of Health. Mucopolysaccharidoses. Accessed November 7, 2024. https://www.ninds.nih.gov/health-information/disorders/mucopolysaccharidoses
  4. Sidhu NS, Schreiber K, Pröpper K, et al. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA. Acta Crystallogr D Biol Crystallogr. 2014;70(Pt 5):1321-1335.
  5. Leal AF, Benincore-Flórez E, Rintz E, et al. Mucopolysaccharidoses: cellular consequences of glycosaminoglycans accumulation and potential targets. Int J Mol Sci. 2022;24(1):477.
  6. Zelei T, Csetneki K, Vokó Z, Siffel C. Epidemiology of Sanfilippo syndrome: results of a systematic literature review. Orphanet J Rare Dis. 2018;13(1):53.
  7. Çelik B, Tomatsu SC, Tomatsu S, Khan SA. Epidemiology of mucopolysaccharidoses update. Diagnostics (Basel). 2021;11(2):273.
  8. Puckett Y, Mallorga-Hernández A, Montaño AM. Epidemiology of mucopolysaccharidoses (MPS) in United States: challenges and opportunities. Orphanet J Rare Dis. 2021;16(1):241.