Proteoglycans disorders

F-1) The mucopolysaccharidoses are proteoglycan disorders that generally result from a hereditary lysosomal defect in enzymes that normally degrade mucopolysaccharides (in most cases heparan sulfate and dermatan sulfate). This leads to the accumulation of different mucopolysaccharides, which may be associated with a variety of different findings, commonly including mental retardation and various skeletal abnormalities. These diseases include Hunter disease, Hurler and Scheie disease, I-cell disease , Maroteaux-Laury disease, Morquio syndrome, Mucolipidoses VH disease, multiple sulfatase deficiency, and Sanfilippo A and B diseases, which will not be elaborated on further here. Often these conditions can be detected in advance on amniocentesis. 

The test system described above is also of use for assessment of clinical conditions for proteoglycan disorders (see Section 7, p. 50) and for monitoring therapy. For example, a proteoglycan disorder has been demonstrated in lipoid proteinosis, but the rectification of abnormal [ °S]sul-fate incorporation was accompanied by clinical improvement (BIO). 

Whereas a considerable number of conditions has been reported to involve proteoglycan disorders in some way or other, the course of development of investigations has been greatly influenced, and dramatically limited to a narrow compass, by various phenomena. First, much of the work reported is derived from studies carried out more than ten... 

It has not been easy to devise a satisfactory structure for this Section, since the information available to date falls far short of permitting any classification of proteoglycan-involving disorders. Sectionalization on the basis of clinical presentation of the disorder or the location of the disorder is impossible since it is uncertain which clinical features are the result of primary disorders and indeed whether or not the proteoglycan disorder is a primary effect. The choice of sectionalization is therefore one based on the location of presentation of proteoglycan disorder. 

Glycosylation disorders represent a constellation of diseases that result from defects in the synthesis of carbohydrate strnctures (glycans) and in the attachment of glycans to other compounds. These defective processes involve the A-linked and O-linked glycosylation pathways, biosynthesis of proteoglycans, as well as lipid glycosylation pathways. 

These disorders are rare collectively, they may occur in 1 in 20,000 live births. Since proteoglycans are widely distributed in human tissues, the syndromes can affect a wide variety of tissues thus, the clinical features vary considerably. All types are characterized by reduced life expectancy, with the exception of Scheie s syndrome. All types are characterized by skeletal abnormalities, which are particularly severe in types IV and VI. Types IH, IS, IV, VI, and VII usually exhibit clouding of the... 

Reviews on disorders with respect to proteoglycan components are... 

Cartilaginous and Skeletal Presentation of Proteoglycan AND Glycosaminoglycan Disorders... 

Body Fluid Pbesentation of Proteoglycan and Glycosaminoclycan Disorders... 

Some disorders of proteoglycan metabolism, e.g. Hurler s syndrome, have been shown to be enzyme-deficiency diseases in which a lysosomal enzyme is missing (page 203). 

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