Mucopolysaccharidosis I

Authors: Lorne A Clarke

Publish Date: 2007

Volume: , Issue: , Pages: 389-405

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Abstract

Mucopolysaccharidosis type I MPS I has historically been considered to represent the prototypical generalized storage disease As such insights provided by clinical observations therapeutic attempts and the understanding of the molecular basis of disease pathophysiology of this disease are likely to be applicable to most of the generalized lysosomal disorders The detailed delineation of the natural history of this disorder has been particularly instructive Deficiency of the lysosomal enzyme αLiduronidase IDUA EC 32176 is the primary defect in MPS I Interestingly the initial clinical classification of the MPSs included a separate group of patients classified as MPS V McKusick et al 1965 It was not until the lysosomal enzyme iduronidase was discovered that it soon became known that MPS I Hurler syndrome and MPS V Scheie syndrome patients had the same primary metabolic defect Wiesmann and Neufeld 1970 The clinical distinctiveness of the two groups related to the fact that they represented opposite ends of a wide clinical disease spectrum This concept of “disease spectrum” is now considered universal in the lysosomal storage disorders LSDs For most of the LSDs this disease spectrum is caused primarily by different mutations within the gene coding for the deficient hydrolase or transporter that is allelic heterogeneity On the other hand observations in Gaucher disease Beutler et al 2004 Zhao et al 2003 Beutler 2001 and Fabry disease Germain et al 2002 AshtonProlla et al 2000 Knol et al 1999 indicate that significant clinical heterogeneity can be seen for patients that have identical mutations These disorders indicate the likelihood of modifier genes that modulate the disease phenotype Detailed understanding of the molecular basis of the LSDs will reveal important insights into the various mechanisms that underlie clinical heterogeneity The genotypephenotype observations for MPS I have been particularly instructive in this regard as will further insights into the identification of factors that modify the disease severity of other lysosomal disorders

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