Summary
We analysed urine and tissue specimens from two nephrotic infantile sialic acid storage disease patients (nISSD) for free and bound sialic acids in comparison to non-nephrotic ISSD patients (ISSD), patients with minimal change nephrosis (nControl) and normal controls (Control). No differences in the excretion of urinary free sialic acid could be detected between ISSD and nISSD urines. Sialyloligosaccharide fractions were only slightly elevated and of apparently normal composition. Owing to glomerular dysfunction, measurable quantities of protein-bound sialic acids were present in nISSD and nControl.
In nISSD tissues, free sialic acid was elevated 18–100-fold above control and 3–12-fold above Niemann-Pick A (NPA) samples. The storage of membrane-bound sialic acid was slightly increased compared to control tissues, but equal to those from NPA, thus reflecting an unspecific increase of membranes due to lysosomal storage.
According to these results no major biochemical differences were detectable between ISSD and nISSD. The nephrotic syndrome in nISSD could not be related to a general deficit in the sialylation of glycoproteins. Nevertheless, a cell membrane-specific alteration in sialoglycoproteins of glomerular cells might still be possible.
Similar content being viewed by others
References
Aylsworth, A. S., Thomas, G. H., Hood, J. L., Malouf, N. and Libert, J. A severe infantile sialidosis: clinical biochemical and microscopic features.J. Pediatr. 96 (1980) 662–668
Baumkötter, J., Cantz, M., Mendla, K., Baumann, W., Friebolin, H., Gehler, J. and Spranger, J. N. Acetylneuraminic storage disease.Hum. Genet. 71 (1985) 155–159
Blau, E. B. and Haas, J. E. Glomerular sialic acid and proteinuria in human renal disease.Lab. Invest. 28 (1973) 477–481
Brenner, B. M., Hostetter, T. H. and Humes, H. D. Molecular basis of proteinuria of glomerular origin.N. Engl. J. Med. 15 (1978) 826–833
Durand, P., Gatti, R., Cavalieri, S., Borrone, C., Tondeur, M., Michalski, J.-C. and Strecker, G. Sialidosis (mucolipidosis I).Helv. Paediatr. Acta 32 (1977) 391–400
Gahl, W. A., Renlund, M. and Thoene, J. G. Lysosomal transport disorders: cystinosis and sialic acid storage disorders. In Scriver, C. R., Beaudet, A. L., Sly, W.S. and Valle, D. (eds.)The Metabolic Basis of Inherited Disease, 6th edn., McGraw-Hill, New York, 1989, pp. 2619–2648
Gruber, W., Paschke, E., Ring, E., Sperl, W. and Stöckler, S. Infantile sialic acid storage disease (ISSD) in two sibs with severe nephrotic syndrome.Eur. J. Pediatr. 146 (1987) 102
Hancock, L. W., Horwitz, A. L. and Dawson, G.N-Acetylneuraminic acid and sialoglycoconjugate metabolism in fibroblasts from a patient with generalizedN-acetylneuraminic acid storage disease.Biochim. Biophys. Acta 760 (1983) 42–52
Kashtan, G. A., Nevins, T. E., Posalaky, Z., Vernier, R. L. and Fish, A. J. Proteinuria in a child with sialidosis: case report and histological studies.Pediatr. Nephrol. 3 (1989) 133–174
Kato, Y., Komiya, K., Sasaki, H. and Hashimoto, T. Comparison of TSK-GEL PW type and SW type in high-speed aqueous gel-permeation chromatography.J. Chromatogr. 193 (1980) 311–315
Kaysen, G. A., Myers, B. D., Couser, W. G., Rabkin, R. and Felts, J. M. Biology of disease. Mechanisms and consequences of proteinuria.Lab. Invest. 54 (1986) 479–498
Kelly, T., Bartoshevsky, L., Harris, D., McCauley, R., Feingold, M. and Schott, G. Mucolipidosis I (acid neuraminidase deficiency).Am. J. Dis. Child. 135 (1981) 703–708.
Kerjaschki, D., Poczewski, H., Dekan, G., Horvat, R., Balzar, E., Kraft, N. and Atkins, R. C. Identification of a major sialglycoprotein in the glycocalyx of human visceral epithelial cells.J. Clin. Invest. 78 (1986) 1142–1149
Mancini, G. M. S., de Jonge, H. R., Galjaard, H. and Verheijen, F. W. Characterization of a proton-driven carrier for sialic acid in the lysosomal membrane.J. Biol. Chem. 264 (1989) 15247–15254
Maroteaux, P., Humbel, R. and Strecker, G. Un nouveau type de sialidose avec atteinte renal: la nephrosialidose.Arch. Franc. Pediatr. 35 (1978) 819–829
Mendla, K., Baumkötter, J., Rosenau, C., Ulrich-Bott, B. and Cantz, M. Defective lysosomal release of glycoprotein-derived sialic acid in fibroblasts from patients with sialic acid storage disease.Biochem. J. 250 (1988) 261–267
Paschke, E., Höfler, G. and Roscher, A. Infantile sialic acid storage disease: the fate of biosynthetically labeled [3H]neuraminic acid in cultured human fibroblasts.Pediatr. Res. 20 (1986a) 773–777
Paschke, E., Trinkl, G., Erwa, W., Pavelka, M., Mutz, I. and Roscher, A. Infantile type of sialic acid storage disease.Clinc. Genet. 29 (1986b) 417–424
Paschke, E., Höfler, G. and Roscher, A. The effect ofD-(+)-glucosamine on levels of freeN-acetylneuraminic acid and UDP-N-acetylhexosamines in infantile sialic acid storage disease (ISSD) fibroblasts.J. Inher. Metab. Dis. 10 (1987) 48–51
Pennock, C. A. A review and selection of simple laboratory methods used for the study of glycosaminoglycan excretion and the diagnosis of the mucopolysaccharidoses.J. Clin. Pathol. 29 (1976) 111–123
Pueschel, S. M., O'Shea, P. A., Alroy, J., Ambler, M. W., Dangond, F., Daniel, P. F. and Kolodny, E. H. Infantile sialic acid storage disease associated with renal disease.Pediatr. Neurol. 4 (1988) 207–212
Renlund, M., Chester, M. A., Lundblad, A., Parkkinen, J. and Krusius, T. FreeN-acetylneuraminic acid in tissues in Salla diseases and the enzymes involved in its metabolism.Eur. J. Biochem. 130 (1983) 39–45
Renlund, M., Kovanen, P., Raivio, K. O., Aula, P., Gahmberg, C. G. and Ehnholm, C. Studies on the defect underlying the lysosomal storage of sialic acid in Salla disease. Lysosomal accumulation of sialic acid formed fromN-acetylmannosamine or derived from low density lipoprotein in cultured mutant fibroblasts.J. Clin. Invest 77 (1986a) 568–574
Renlund, M., Tietze, F. and Gahl, W. Defective sialic acid egress from isolated fibroblast lysosomes of patients with Salla disease.Science 232 (1986b) 759–762
Roth, K. S., Chan, J. C., Ghatak, N. R., Mamunes, P., Miller, W. W. and O'Brien, J. S. Acid α-neuraminidase deficiency: a nephropathic phenotype?Clin. Genet. 34 (1988) 185–194
Schauer, R. and Corfield, A. P. Colorimetry and thin-layer chromatography of sialic acids. In Schauer, R. (ed.)Sialic Acids. Chemistry, Metabolism and Function, Springer Verlag, Wien, New York, 1982, pp. 77–94
Skoza, L. and Mohos, S. Stable thiobarbituric acid chromophore with dimethylsulphoxide. Application to sialic acid assay in analytical de-O-acetylation.Biochem. J. 159 (1976) 457–462
Sperl, W., Gruber, W., Quatacker, J., Monnens, L., Thoenes, W., Fink, F. M. and Paschke, E. Nephrosis in two siblings with infantile sialic acid storage disease.Eur. J. Pediatr. 149 (1990) 477–482
Taylor, J., Thorner, P., Geary, D. F., Baumal, R. and Balfe, J. W. Nephrotic syndrome and hypertension in two children with Hurler syndrome.J. Pediatr. 108 (1986) 726–729
Tietze, F., Seppala, R., Renlund, M., Hopwood, J. J., Harper, G. S., Thomas, G. H. and Gahl, W. A. Defective lysosomal egress of free sialic acid (N-acetylneuraminic acid) in fibroblasts of patients with infantile free sialic acid storage disease.J. Biol. Chem. 264 (1989) 15316–15322
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Paschke, E., Gruber, W., Ring, E. et al. Storage material from urine and tissues in the nephropathic phenotype of infantile sialic acid storage disease. J Inherit Metab Dis 15, 47–56 (1992). https://doi.org/10.1007/BF01800343
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01800343