IDUA encodes alpha-L-iduronidase, a lysosomal hydrolase essential for glycosaminoglycan (GAG) catabolism, specifically degrading dermatan sulfate and heparan sulfate 1. The enzyme functions in the lysosomal lumen to catalyze disaccharide metabolism and proteoglycan breakdown. IDUA deficiency causes mucopolysaccharidosis type I (MPS I), a lysosomal storage disorder with three phenotypic variants: severe Hurler disease with CNS involvement, intermediate Hurler/Scheie disease, and mild Scheie disease without cognitive impairment 1. Disease severity correlates poorly with genotype, though homozygous nonsense mutations typically produce Hurler phenotype 1. Over 200 pathogenic variants exist, with p.Trp402Ter, p.Gln70Ter, and p.Pro533Arg being geographically common 2. MPS I presents with progressive skeletal dysostosis multiplex, airway obstruction, corneal clouding, joint contractures, cardiac valve disease, and hepatosplenomegaly 1. IDUA deficiency also causes cardiac complications including cardiomyopathy and arrhythmias 3. Treatment options include enzyme replacement therapy (laronidase), which improves GAG excretion and respiratory function, and hematopoietic stem cell transplantation, which can stabilize cognitive decline when performed early 1. Emerging gene therapy approaches using lentiviral vectors to deliver functional IDUA in autologous hematopoietic stem cells show promising results, achieving supraphysiologic enzyme activity and metabolic correction in both peripheral tissues and CNS 4.