PathwayStep1110 PathwayStep4258 Defective IDUA does not hydrolyse Lido Glycosaminoglycan metabolism MPS I - Hurler syndrome Authored: Jassal, B, 2012-04-26 Edited: Jassal, B, 2012-04-26 Mucopolysaccharidosis type I (MPS I, Hurler syndrome, Hurler's disease, gargoylism, Scheie, Hirler-Scheie syndrome; MIM:607014, 607015 and 607016) is an autosomal recessive genetic disorder where there is a deficiency of alpha-L iduronidase (IDUA, MIM:252800), a glycosidase that removes non-reducing terminal alpha-L-iduronide residues during the lysosomal degradation of the glycosaminoglycans heparan sulphate and dermatan sulphate (McKusick 1959). In 1992, Scott and colleagues were able to clone and purify the gene that encodes this enzyme, IDUA, demonstrating that it spans approximately 19 kb and contains 14 exons (Scott et al. 1992).<br>Hurler syndrome is named after a German paediatrician Gertrud Hurler (1919, no reference available). The result is build up of heparan sulfate and dermatan sulfate in the body and increased urinary excretion of these GAGs. Symptoms and signs include hepatosplenomegaly, dwarfism, unique facial features, corneal clouding, retinopathy, progressive mental retardation appears during childhood and early death can occur due to organ damage (Campos & Monaga 2012). MPS I is divided into three subtypes, ranging from severe to mild phenotypes; Mucopolysaccharidosis type IH (MPSIH, Hurler syndrome, MIM:607014), mucopolysaccharidosis type IH/S (MPSIH/S, HurlerScheie syndrome, MIM: 607015) and mucopolysaccharidosis type IS (MPSIS, Scheie syndrome, MIM: 607016) respectively (McKusick 1972). Pubmed13629198 Pubmed1505961 Pubmed22527994 Pubmed4112371 Reactome Database ID Release 432206302 Reactome, http://www.reactome.org ReactomeREACT_147857 Reviewed: Alves, Sandra, 2012-08-27 Reviewed: Ashworth, Jane, 2012-08-28 Reviewed: Coutinho, Maria, 2012-08-27