Glycosaminoglycans and mucopolysaccharidosis type III.
Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is a lysosomal storage disease in which heparan sulfate is accumulated in lysosomes, as well as outside of cells, as the primary storage material. This disease is a complex of four conditions caused by dysfunctions of one of genes coding for lysosomal enzymes involved in degradation of heparan sulfate: SGSH (coding for heparan N-sulfatase) - causing MPS IIIA, NAGLU (coding for alpha-N-acetylglucosaminidase) - causing MPS IIIB, HGSNAT (coding for acetyl CoA alpha-glucosaminide acetyltransferase) - causing MPS IIIC), and GNS (coding for N-acetylglucosamine-6-sulfatase) - causing MPS IIID. The primary storage is responsible for some disease symptoms, but other arise as a result of secondary storage, including glycosphingolipids, and subsequent processes, like oxidative stress and neuroinflammation. Central nervous system is predominantly affected in all subtypes of MPS III. Heparan sulfate and its derivatives are the most commonly used biomarkers for diagnosis and prediction procedures. Currently, there is no therapy for Sanfilippo syndrome, however, clinical trials are ongoing for enzyme replacement therapy, gene therapy and substrate reduction therapy (particularly gene expression-targeted isoflavone therapy).
Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
Joanna
J
Jakobkiewicz-Banecka
Laboratory of Molecular Biology (affiliated with the University of Gdansk), Instituite of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdansk, Poland.
Magdalena
M
Gabig-Ciminska
Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
Anna
A
Kloska
Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
Marcelina
M
Malinowska
Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
Ewa
E
Piotrowska
Department of Neurology, Medical University of Gdansk, Debinki 7, 80-211 Gdansk, Poland.
Zyta
Z
Banecka-Majkutewicz
Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland.
Bogdan
B
Banecki
Laboratory of Molecular Biology (affiliated with the University of Gdansk), Instituite of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdansk, Poland.
Alicja
A
Wegrzyn
Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland, grzegorz.wegrzyn@biol.ug.edu.pl.
Grzegorz
G
Wegrzyn
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009084:Mucopolysaccharidosis III / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D009154:Mutation
D015415:Biomarkers; D006025:Glycosaminoglycans; D006497:Heparan Sulfate