The involvement of a variety of glycoconjugates in the biochemical pathogenesis of inherited diseases with progressive degenerative mental retardation will be analyzed and evaluated. A rapid, sensitive and accurate method will be devised for the identification and quantification of glycopeptides and oligosaccharides with high performance liquid chromatography. This method will be developed to facilitate diagnosis and screening of selected oligosaccharide storage diseases in humans; GM1 gangliosidosis, Sandhoff disease, aspartylglucosaminuria, sialidosis, Alpha-mannosidosis, I-cell disease, pseudo-Hurler polydystrophy, Alpha-fucosidosis, and unusual variants thereof. Urine or aminiotic fluid will be employed as specimen sources for antenatal and postnatal diagnosis of these disorders. Patients with undiagnosed cerebral degeneration will also be screened in this study. The functional relationship between stored and/or excreted oligosaccharides and unique clinical phenotypic features within these disease subtypes will be evaluated. Variations in oligosaccharide levels and species will be monitored over the course of canine GM1 gangliosidosis. Detailed structure analysis will be carried out on oligosaccharides of interest using high resolution nuclear magnetic resonance spectroscopy, permethylation and GC-mass spectral analysis. The biochemical pathways of glycoconjugate degradation and catabolism will be investigated in these disorders and in normals.
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