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.