Mucopolysaccharidoses genetics

The GAGs are synthesized by the sequential actions of a battery of specific enzymes (glycosyltransferases, epimerases, suhotransferases, etc) and are degraded by the sequential action of lysosomal hydrolases. Genetic deficiencies of the latter result in mucopolysaccharidoses (eg, Hurler syndrome). 

Byers S, Rozaklis T, Brumfield LK, Ranieri E, Hopwood JJ (1998) Glycosaminoglycan accumulation and excretion in the mucopolysaccharidoses characterization and basis of a diagnostic test for MPS. Mol Genet Metab 65 282-290... 

Dembure PP, Roesel RA (1991) Screening for mucopolysaccharidoses by analysis of urinary glycosaminoglycans. In Hommes FA (ed) Techniques in Diagnostic Human Biochemical Genetics. Wiley-Liss, New York, pp 77-86... 

Genetic defects in the degradation of glycoproteins are representative of lysosomal storage disorders. Each disease is caused by a deficiency of a lysosomal hydrolase, accumulation and urinary excretion of substrates, a progressive clinical course and considerable phenotypic variation. These disorders also manifest the clinical symptoms normally associated with genetic mucopolysaccharidoses, namely coarse facies, dysostosis multiplex and/or ocular involvement. 

Sulfotransferases917 920a transfer sulfo groups to O and N atoms of suitable acceptors (reaction type ID, Table 10-1). Usually, transfer is from the "active sulfate," 3 -phosphoadenosine 5 -phosphosuIfate (PAPS),921 whose formation is depicted in Eq. 17-38. Sulfatases catalyze hydrolysis of sulfate esters. The importance of such enzymes is demonstrated by the genetic mucopolysaccharidoses. In four of these disease-specific sulfatases that act on iduronate sulfate, heparan N-sulfate, galactose-6-sulfate, or N-acetylglu-cosamine-4-sulfate are absent. Some of these, such as heparan N-sulfatase deficiency, lead to severe mental retardation, some cause serious skeletal abnormalities, while others are mild in their effects.922... 

Analysis of urine for excess substrates (e.g., glycosaminoglycans in the Mucopolysaccharidoses, globotriaolsylceramide in Fabry disease) may also suggest the presence of an LSD. In any case, all patients suspected to have an LSD should have diagnostic confirmation by means of biochemical and/or molecular genetic analysis. 

Mucopolysaccharidoses occur when there is a genetic deficiency of the enzymes involved in the lysosomal breakdown of the glycosaminoglycans. 

A number of genetic diseases associated with proteoglycan metabolism, known as mucopolysaccharidoses, have been identified. Because proteoglycans are con-... 

N2. Nmt5, V., and Friman, C., Electrophoretic analysis of urinary glycosamino-glycans in genetic mucopolysaccharidoses. Scand. J. Clin. Lab. Inwst. 29, Suppl. 123, 25 (1972). 

Sabater, J., Villalba, M., and Maya, A, Mass screening newborns for mucopolysaccharidoses. Clin. Genet. 4, 260-263 (1973). 

Functions. — A survey of which enzymes are lacking in cases of genetic hyper-glycosaminoglycanuria (mucopolysaccharidoses) has been made. A novel mechanism has been demonstrated for the introduction of hydrolytic enzymes into the lysosomes of fibroblasts in cell culture by a secretion and capture process. 

As part of a study on the neurochemistry of the genetic hyperglycoamino-glycanuria conditions (mucopolysaccharidoses), lysosomal enzymes including a- and j8-D-galactosidases in patients of four types and normals have been investigated in brain and liver. ... 

Cantz, M., and Gehler, J., 1976, The mucopolysaccharidoses Inborn errors of glycosa-minoglycan catabolism. Hum. Genet. 32 233. 

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