title: Correlation between severity of mucopolysaccharidoses and combination of the residual enzyme activity and efficiency of glycosaminoglycan synthesis.
abstract: OBJECTIVE
  To develop a method for prediction of severity and clinical course of mucopolysaccharidoses (MPS), a group of inherited metabolic diseases.
  
  
  METHODS
  Various biochemical and clinical parameters (including estimation of the level of clinical severity, presence of specific mutations, residual enzyme activity, urinary glycosaminoglycan (GAG) excretion, storage of GAG in fibroblasts and efficiency of GAG synthesis) of patients suffering from MPS types II, IIIA and IIIB were determined. Correlations between genetic, biochemical and clinical parameters were tested.
  
  
  RESULTS
  We found that efficiency of GAG synthesis may contribute to the level of severity of MPS. It appears that (i) combination of low or average efficiency of GAG synthesis and the presence of residual activity of the enzyme is responsible for an attenuated phenotype, (ii) a lack of detectable residual enzyme activity causes a severe phenotype, irrespective of the efficiency of GAG synthesis and (iii) high efficiency of GAG synthesis leads to a severe phenotype, even if residual enzyme activity is detected. This correlation was found to be valid in 15 out of 17 patients tested.
  
  
  CONCLUSIONS
  Analysis of efficiency of GAG synthesis and residual activity of the enzyme may be considered for prediction of severity of MPS patients' clinical phenotypes.
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Piotrowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakóbkiewicz-Banecka
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymańska
authors.forename: Barbara
authors.initials: B
authors.lastname: Czartoryska
authors.forename: Alicja
authors.initials: A
authors.lastname: Wegrzyn
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wegrzyn
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis* / Q000378:metabolism / Q000652:urine; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009083:Mucopolysaccharidoses / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D009154:Mutation; D010641:Phenotype; D011379:Prognosis
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans