Summary
Human β-galactosidase and α-neuraminidase deficient mucolipidosis [ML(gal-neur-)] is an inherited lysosomal enzymopathy which recently was designated as a sialidosis. We analyzed the neuraminidase deficiency of this disorder with genetic complementation analyses using a heterokaryon enrichment procedure. The genetic defects of two apparent variants of this disorder complemented the defects of the neuraminidase deficiency diseases, sialidosis I and mucolipidosis I, resulting in the restoration of neuraminidase activity in heterokaryons. The neuraminidase deficiency, therefore, may not be the primary defect in ML(gal-neur-) and is not an appropriate test for determining carrier status. The clinical and biochemical characteristics of this disorder suggest that a post-translational or processing event for these enzymes may be defective. The defect, however, is different from I-cell disease and pseudo-Hurler polydystrophy, two disorders of post-translational lysosomal enzyme biosynthesis, since complementation studies demonstrated recovery of intracellular β-galactosidase and α-neuraminidase levels in heterokaryons. The lack of human β-galactosidase expression in man-mouse somatic cell hybrids formed from fibroblasts of the infantile onset type disorder suggests that the defect is not corrected by the mouse genome. The ML(gal-neur-) disorder therefore appears to be a distinct subtype of the inherited neuraminidase deficiencies in which the defect may occur in a post-translational or regulatory step which coordinately affects the expression of lysosomal β-galactosidase and α-neuraminidase.
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References
Andria G, Del Giudice E, Reuser AJJ (1978) Atypical expression of β-galactosidase deficiency in a child with Hurler-like features but without neurological abnormalities. Clin Genet 14:16–23
Ashwell G, Morell AG (1974) The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol 41:99–128
Bruns GAP, Mintz BJ, Leary AC, Regina VM, Gerald PS (1979) Human lysosomal genes: Arylsulfatase A and β-galactosidase. Biochem Genet 17:1031–1059
Champion MJ, Shows TB (1977) Correction of human mucolipidosis II enzyme abnormalities in somatic cell hybrids. Nature 270:64–66
d'Azzo A, Halley DJJ, Hoogeveen A, Galjaard H (1980) Correction of I-cell defect by hybridization with lysosomal enzyme deficient human fibroblasts. Am J Hum Genet 32:519–528
de Wit J, Hoeksema HL, Bootsma D, Westerveld A (1979) Assignment of structural β-galactosidase loci to human chromosomes 3 and 22. Hum Genet 51:259–267
Galjaard H, Hoogeveen A, Keijzer W, de Wit-Verbeek HA, Reuser AJJ, Ho MW, Rohinson D (1975) Genetic heterogeneity in GMI-gangliosidosis. Nature 257:60–62
Goldberg MF, Cotlier E, Fichenscher LG, Kenyon K, Enat R, Borowsky SA (1971) Macular cherry-red spot, corneal clouding, and β-galactosidase deficiency. Arch Intern Med 128:387–398
Gravel RA, Gravel YL, Miller AL, Lowden JA (1981) Genetic complementation analysis of I-cell disease and pseudo-Hurler polydystrophy. In: Callahan JW, Lowden JA (eds) Lysosomes and lysosomal storage diseases. Raven Press, New York, p 289
Hoeksema HL, van Diggelen OP, Galjaard H (1979) Intergenic complementation after fusion of fibroblasts from different patients with β-galactosidase deficiency. Biochim Biophys Acta 566:72–79
Hoeksema HL, De Wit J, Westerveld A (1980) The genetic defect in various types of human β-galactosidase deficiency. Hum Genet 53: 241–247
Honey NK, Miller AL, Shows TB (1981a) The mucolipidoses: Identification by abnormal electrophoretic patterns of lysosomal hydrolases. Am J Med Genet 9:239–253
Honey NK, Mueller OT, Miller AL, Shows TB (1981b) Genetic heterogeneity within pseudo-Hurler polydystrophy. Am J Hum Genet 33: 142A
Hoogeveen AT, Verheijen FW, d'Azzo A, Galjaard H (1980) Genetic heterogeneity in human neuraminidase deficiency. Nature 285: 500–502
Karig Hohmann L., Shows TB (1979) Complementation of genetic disease: A velocity sedimentation procedure for the enrichment of heterokaryons. Somatic Cell Genet 5:1013–1029
Kato T, Okada S, Yutaka T, Inui K, Yabuuchi H, Chiyo H, Furuyama J, Okada Y (1979) Beta-galactosidase deficient-type mucolipidosis: A complementation study of neuraminidase in somatic cell hybrids. Biochem Biophys Res Commun 91:114–117
Lowden JA, O'Brien JS (1979) Sialidosis: A review of human neuraminidase deficiency. Am J Hum Genet 31:1–18
Lowry OH, rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Miyatake T, Atsumi T, Obayashi T, Mizuno Y, Ando S, Ariga T, Matsui-Nakamura K, Yamada T (1979) Adult type neuronal storage disease with neuraminidase deficiency. Ann Neurol 6:232–244
Mueller OT, Wenger DA (1981) Mucolipidosis I: Studies of sialidase activity and a prenatal diagnosis. Clin Chim Acta 109:313–324
Mueller OT, Honey NK, Miller AL, Shows TB (1981) Genetic dissection of I-cell disease and pseudo-Hurler polydystrophy: Disorders of lysosomal enzyme processing. Am J Hum Genet 33:50A
Norden AGW, O'Brien JS (1974) Binding of human liver β-galactosidases to plant lectins insolubilized on agarose. Biochem Biophys Res Commun 56:193–198
Norwood TH, Zeigler CJ, Martin GM (1976) Dimethyl sulfoxide enhances polyethylene glycol-mediated somatic cell fusion. Somatic Cell Genet 2:263–270
O'Brien JS (1975) Molecular genetic of GM1β-galactosidase. Clin Genet 8:303–313
Okada S, Kato T, Miura S, Yabuuchi H, Nishigaki M, Kobata A, Chiyo H, Furuyama J (1978) Hypersialyloligosacchariduria in mucolipidoses: A method for diagnosis. Clin Chim Acta 86:159–167
Okada S, Kato T, Yabuuchi H, Okada Y (1979) The complementation of β-galactosidase in fused cells of mucolipidosis II with another variants of β-galactosidase deficiency using new single cell enzyme assay. Biochem Biophys Res Commun 88:559–562
Orii T, Minami R, Sukegawa K, Sato S, Tsugawa S, Horino K, Miura R, Nakao T (1972) A new type of mucolipidosis with β-galactosidase deficiency and glycopeptiduria. Tohuku J Exp Med 107:303–315
Shows TB (1972) Genetics of human-mouse somatic cell hybrids: Linkage of human genes for lactate dehydrogenase-A and esterase-A4. Proc Natl Acad Sci USA 69:348–352
Shows TB, Scrafford-Wolff LR, Brown JA, Meisler MH (1979) GM1-Gangliosidosis: Chromosome 3 assignment of the β-galactosidase-A gene (βGAL A). Somatic Cell Genet 5:147–158
Shows TB, Mueller OT, Honey NK, Wright CE, Miller AL (1982) Genetic heterogeneity within I-cell disease is demonstrated by complementation of lysosomal enzyme processing mutants. Am J Med Genet (in press)
Suzuki Y, Nakamura N, Fukuoka K, Shimada Y, Uono M (1977) β-Galactosidase deficiency in juvenile and adult patients. Hum Genet 36:219–229
Swallow DM, Hoogeveen AT, Verheijen FW, Galjaard H (1981) Complementation analysis of human sialidase deficiency using natural substrates. Ann Hum Genet 45:105–112
Thomas GH, Tipton RE, Ch'ien LT, Reynolds LW, Miller CS (1978) Sialidase (α-N-acetyl neuraminidase) deficiency: The enzyme defect in an adult with macular cherry-red spots andmyoclonus without dementia. Clin Genet 13:369–379
Thomas GH, Goldberg MF, Miller CS, Reynolds LW (1979) Neuraminidase deficiency in the original patient with the Goldberg syndrome. Clin Genet 16:323–330
Warner TG, O'Brien JS (1979) Synthesis of 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid and detection of skin fibroblast neuraminidase in normal humans and in sialidosis. Biochemistry 18: 2783–2787
Wenger DA, Tarby TJ, Wharton C (1978) Macular cherry-red spots and myoclonus with dementia: Coexistent neuraminidase and β-galactosidase deficiencies. Biochem Biophys Res Commun 82:589–595
Wright CE, Miller AL, Shows TB (1979) Complementation analysis of the mucolipidoses demonstrates genetic heterogeneity. Am J Hum Genet 31:66A
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Mueller, O.T., Shows, T.B. Human β-galactosidase and α-neuraminidase deficient mucolipidosis: Genetic complementation analysis of the neuraminidase deficiency. Hum Genet 60, 158–162 (1982). https://doi.org/10.1007/BF00569704
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DOI: https://doi.org/10.1007/BF00569704