MUCOPOLYSACCHARIDOSIS TYPE-VII (SLYS DISEASE)

Mucopolysaccharidosis Type VII (MPS VII, Sly's disease) is one of a gr oup of inherited storage diseases, the mucopolysaccharidoses, caused b y defects in lysosomal enzymes that degrade glycosaminoglycans (GAGs) (mucopolysaccharides). Individuals with MPS VII have a deficiency in b eta-glucuronidase which results in accumulation of uncatabolized GAGs in multiple organs, Clinically, MPS patients commonly present with pro gressive neurologic dysfunction, visceromegaly, and skeletal dysostosi s, Diagnosis of MPS includes recognition of the pathophysiological fea tures common in MPS patients and determination of the specific underly ing enzymatic defect, More recently, genetic analysis of MPS VII patie nts allows for the precise determination of the genetic lesion, Mutati ons identified in the GUSB gene (gene coding for beta-glucuronidase) c orrelate with phenotypic severity, Introduction of the GUSB gene into a murine model for MPS VII corrects the genetic defect, The ability to analyze and manipulate genes enhances classical diagnostic and progno stic techniques, with the ultimate goal being the correction of inborn errors of metabolism, Postmortem biochemical and pathological finding s from the first patient in whom MPS VII was described in 1973 are pre sented here, as are current and future strategies for enzyme replaceme nt and gene therapy using MPS VII as a model.