Accumulation of glycoprotein-derived metabolites in neural and visceral tissue in aspartylglycosaminuria.

The storage material in various tissues from patients with inherited deficiency of lysosomal aspartylglucosamine amidohydrolase (aspartylglycosaminuria) was characterized by gas chromatographic-mass spectrometric analyses of intact and specifically degraded derivatives. The major storage compound in cerebral gray and white matter, spinal cord, sciatic nerve, spleen, kidney, skeletal muscle and thyroid gland was identified as 2-acetamido-l-N-(4'-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (GlcNAc-Asn). Thin-layer chromatography revealed an additional glycoasparagine band in spleen, kidney, thyroid, and brain. The compound was purified from spleen, and its structure is tentatively proposed to be D-mannopyranosyl-(1-6)-D-mannopyranosyl (1-4)-2-acetamido-2-deoxy-D-glucopyranosyl-(1-4)-2-acetamido-l-N-(4'-L-aspartyl )-2-deoxy-beta-D-glucopyranosylamine (Man2-GlcNAc2-Asn). The results show that the major glycoasparagine storage product in both neural and extraneural tissues in aspartylglycosaminuria is GlcNAc-Asn. Furthermore, a more complex glycoasparagine, presumably Man2-GlcNAc2-Asn, accumulates in smaller amounts in tissues of patients with aspartylglycosaminuria.