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Mucopolysaccharidosis
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The mucopolysaccharidoses (MPS) are a family of disorders that
are caused by inherited defects in the catabolism of sulfated components
of connective tissue known as glycosaminoglycans (GAGs).
In affected patients, one or more of three specific polymers—dermatan
sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)—accumulate
within the cells, interfering with normal function, and are excreted
in excess in the urine. The main enzymatic defects in the catabolism
of the GAGs dermatan, heparan, and keratan sulfate are shown in eFigure 160.1.
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The enzymes associated with GAG catabolism are all lysosomal
hydrolases, and patients with an MPS disorder usually have less
than 1% residual enzyme activity. Heterozygote detection
based on enzyme activity alone is inaccurate and is now, fortunately,
no longer necessary, as the genes encoding the enzymes involved
in GAG catabolism have been identified and sequenced. Phenotypic
variability (heterogeneity) is very much a feature of MPS disease,
and within each specific enzyme deficiency there is a very wide
spectrum of clinical effects. Although the disorders are most often
known by their eponymous titles (eg, Hurler syndrome), this has
led to an oversimplification in the classification of the subtypes,
which should be kept in mind when interpreting the data in Table 160-1. A comprehensive review of the
biochemistry and molecular biology of these disorders can be found
in Neufeld and Muenzer, 2001.1
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