Diagnosis and characterization of GM 2 gangliosidosis type II (Sandhoff disease) by analysis of the accumulating N-acetyl-glucosaminyl oligosaccharides with high performance liquid chromatography.

Abstract The N -acetyl-glucosaminyl oligosaccharides excreted in urine and accumulating in tissues of Sandhoff disease patients have been analyzed and characterized using a combination of high performance liquid chromatography and 500 MHz proton magnetic resonance spectroscopy. Delineation between infantile and juvenile onset forms of the disease was possible, as the latter forms had 6- to 13-fold lower levels of urinary oligosaccharides. Patients from a geographically isolated population deme in the La Rioja region of Argentina had urinary oligosaccharides similar to unrelated non-Argentinean patients with identical clinical phenotype. Together, these results indicate that the urinary oligosaccharides serve as useful indicators of the mutation differences or clinical heterogeneity within this disease only in cases of markedly differing clinical presentation. Analysis of the accumulating metabolites in liver, kidney, pancreas, lung and spleen, showed a similar oligosaccharide pattern which differed dramatically from brain. These results suggest the possibility of tissue specific regulation of oligosaccharide biosynthesis since there are notable differences between neural and visceral tissues.