Mucopolysaccharidosis type I is a rare autosomal recessive genetic disease caused by deficient activity of α-l-iduronidase. As a consequence of low or absent activity of this enzyme, glycosaminoglycans accumulate in the lysosomal compartments of multiple cell types throughout the body. Mucopolysaccharidosis type I has been classified into 3 clinical subtypes, ranging from a severe Hurler form to the more attenuated Hurler–Scheie and Scheie phenotypes. Over 200 gene variants causing the various forms of mucopolysaccharidosis type I have been reported. DNA isolated from dried blood spot was used to sequencing of all exons of the IDUA gene from a patient with a clinical phenotype of severe mucopolysaccharidosis type I syndrome. Enzyme activity of α-l-iduronidase was quantified by fluorimetric assay. Additionally, a molecular dynamics simulation approach was used to determine the effect of the Ser633Trp mutation on the structure and dynamics of the α-l-iduronidase. The DNA sequencing analysis and enzymatic activity shows a c.1898C>G mutation associated a patient with a homozygous state and α-l-iduronidase activity of 0.24 μmol/L/h, respectively. The molecular dynamics simulation analysis shows that the p.Ser633Trp mutation on the α-l-iduronidase affect significant the temporal and spatial properties of the different structural loops, the N-glycan attached to Asn372 and amino acid residues around the catalytic site of this enzyme. Low enzymatic activity observed for p.Ser633Trp variant of the α-l-iduronidase seems to lead to severe mucopolysaccharidosis type I phenotype, possibly associated with a perturbation of the structural dynamics in regions of the enzyme close to the active site.

I型粘多糖贮积病是一种罕见的常染色体隐性遗传疾病，由α- 1-异丁烯酸苷酶活性不足引起。由于这种酶的活性低或缺乏，糖胺聚糖在体内分布于多种细胞类型的溶酶体区室中。I型粘多糖贮积病已分为3种临床亚型，从严重的Hurler形式到更弱化的Hurler-Scheie和Scheie表型。已有200多种导致各种形式的I型粘多糖贮积病的基因变异。从干血斑分离出的DNA用于对患有严重I型粘多糖贮积症临床表现型的患者的IDUA基因的所有外显子进行测序。α- 1的酶活性-异泛酸苷酶通过荧光测定法定量。另外，使用分子动力学模拟方法来确定Ser633Trp突变对α- 1-艾杜糖醛酸酶的结构和动力学的影响。DNA测序分析和酶活性显示c.1898C> G突变与患者纯合状态相关，并且α- 1-异丁烯酸酶活性分别为0.24μmol/ L / h。分子动力学模拟分析表明，α- 1- iduronidase上的p.Ser633Trp突变会显着影响不同结构环，连接于Asn372的N-聚糖以及该酶催化位点周围的氨基酸残基的时空特性。 。对于α-的p.Ser633Trp变体观察到低的酶活性I- iduronididase似乎导致严重的I型粘多糖贮积病表型，可能与靠近活性位点的酶区域的结构动力学紊乱有关。