title: Why are behaviors of children suffering from various neuronopathic types of mucopolysaccharidoses different?
abstract: Mucopolysaccharidoses (MPS) are inherited metabolic disorders from the group of lysosomal storage diseases (LSD). They arise from mutations causing dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs) in lysosomes. Impaired degradation of these compounds results in their accumulation in cells and dysfunction of most tissues and organs of patients. If heparan sulfate (HS) is the sole or one of stored GAGs, brain functions are also affected. However, despite the fact that products of incomplete degradation of the same chemical, HS, are accumulated in brains of patients suffering from Hurler disease (MPS type I), Hunter disease (MPS type II), Sanfilippo disease (MPS type III) and Sly disease (MPS type VII), and obvious deterioration of brain functions occur in these patients, their behavior is considerably different between various types of MPS. Here we asked the question about biochemical reasons of these differences. We performed theoretical analysis of products of incomplete HS degradation that accumulate in tissues of patients diagnosed for these diseases. A correlation between chemical structures of incompletely degraded HS and behaviors of patients suffering from particular MPS types was found. We propose a hypothesis that particular chemical moieties occurring at the ends of incompletely degraded HS molecules may determine characteristic behavioral disturbances, perhaps due to chemical reactions interfering with functions of neurons in the brain. A possible experimental testing of this hypothesis is also proposed. If the hypothesis is true, it might shed some new light on biochemical mechanisms of behavioral problems occurring not only in MPS but also in some other diseases.
authors: Department of Molecular Biology, University of Gdańsk, Kładki 24, 80-822 Gdańsk, Poland. wegrzyn@biotech.univ.gda.pl
authors: Grzegorz
authors: G
authors: Węgrzyn
authors: Joanna
authors: J
authors: Jakóbkiewicz-Banecka
authors: Magdalena
authors: M
authors: Narajczyk
authors: Andrzej
authors: A
authors: Wiśniewski
authors: Ewa
authors: E
authors: Piotrowska
authors: Magdalena
authors: M
authors: Gabig-Cimińska
authors: Anna
authors: A
authors: Kloska
authors: Monika
authors: M
authors: Słomińska-Wojewódzka
authors: Anna
authors: A
authors: Korzon-Burakowska
authors: Alicja
authors: A
authors: Węgrzyn
mesh_terms: D001526:Behavioral Symptoms / Q000209:etiology* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002648:Child; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D009083:Mucopolysaccharidoses / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans