Residual Enzyme Activity Determines Phenotypic Severity In Mucopolysaccharidosis Type I

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by deficiency of the enzyme α-L-iduronidase, which is involved in glycosaminoglycan (GAG) degradation. Accumulation of the GAGs heparan sulfate and dermatan sulphate causes progressive multi-organ dysfunction, including mental retardation and skeletal deformations. Patients present with a continuous spectrum of phenotypic severity, and are usually classified as Hurler (MPSI-H, severe), Hurler-Scheie (MPSI-HS, intermediate) and Scheie syndrome (MPSI-S, attenuated). Haematopoetic stem cell transplantation (HSCT) is the preferred treatment strategy for MPSI-H patients under the age of approximately 2.5 years, while other patients are usually treated with enzyme replacement therapy. However, in order to obtain optimal treatment efficacy, early initiation of therapy is needed and this necessitates early prediction of the phenotype. Genotype is not always informative and assessment of the phenotype based on clinical criteria can be difficult. …