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The AB-variant of GM2-gangliosidosis

Clinical, biochemical, and pathological studies of two patients

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Summary

Clinical, neuropathological, and biochemical studies are reported in two children with the aB-variant of GM2-gangliosidosis. One patient had become symptomatic by 1–1.5 years, initially showing cerebellar signs, and then progressive psychomotor retardation, with hypotonia, spasticity, dementia, and macular cherry red spots, until death at the age of 4.5 years. The second patient showed an earlier onset of retardation and a more rapidly progressive course. At postmortem, the brains were of normal or near normal weights and displayed grossly only mild cerebral cortical and cerebellar atrophy, and mild pallor or attenuation of the white matter. Neuronal storage was widespread throughout the CNS, and both neurons and glia contained a variety of abnormal, membranous inclusions. Visceral organs were not involved. Ganglioside sialic acid was increased several fold in gray matter, with GM2 the predominant ganglioside species. N-acetyl-β-glucosaminidase activities in serum, leukocytes, fibroblasts, and postmortem gray matter, assayed with an artificial, fluorogenic substrate, were normal, as were activities of other lysosomal hydrolases.

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References

  1. Abramson MB, Norton WT, Katzman R (1965) Study of ionic structures in phospholipids by infrared spectra. J Biol Chem 240:2389–2395

    Google Scholar 

  2. Adachi M, Schneck L, Volk BW (1978) Progress in investigations in sphingolipidoses. Acta Neuropathol (Berl) 43:1–18

    Google Scholar 

  3. Adachi M, Torii J, Karvounis PC, Volk BW (1971) Alterations of astrocytic organelles in various lipidoses and allied diseases. Acta Neuropathol (Berl) 18:74–83

    Google Scholar 

  4. Aleu F, Terry RD, Zellweger H (1965) Electron microscopy of two cerebral biopsies in gargoylism. J Neuropathol Exp Neurol 24:304–317

    Google Scholar 

  5. Ando S, Chang N-C, Yu RK (1978) High performance thin layer chromatography and densitometric determination of brain ganglioside composition of several species. Anal Biochem 89:437–450

    Google Scholar 

  6. Brett EM, Ellis RB, Haas L, Ikonne JU, Lake BD, Patrick AD, Stephens R (1973) Late onset GM2-gangliosidosis. Clinical, pathological, and biochemical studies on eight patients. Arch Dis Child 48:775–785

    Google Scholar 

  7. Conzelmann E, Sandhoff K (1978) AB-variant of infantile GM2-gangliosidosis. Deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside Gm2 and glycolipid GA2. Proc Natl Acad Sci USA 75:3979–3983

    Google Scholar 

  8. Conzelmann E, Sandhoff K, Nehrkorn H, Geiger B, Arnon R (1978) Purification, biochemical and immunological characterisation of hexosaminidase A from variant AB of infantile GM2 gangliosidosis. Eur J Biochem 84:27–33

    Google Scholar 

  9. deBaccque CM, Suzuki K, Rapin I, Johnson AB, Whethers DL, Suzuki K (1975) GM2-gangliosidosis AB-variant. Clinico-pathological study of a case. Acta Neuropathol (Berl) 33:207–226

    Google Scholar 

  10. Fischer G, Jatzkewitz H (1975) The activator of cerebroside sulfatase: Purification from human liver and identification as a protein. Z Physiol Chem 356:605–613

    Google Scholar 

  11. Folch-Pi J, Lees MB, Sloane-Stanley GH (1959) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    Google Scholar 

  12. Harrell LS (1966) Tay-Sachs disease (amaurotic familial idiocy) in a non-Jewish male. A case report. J Am Osteopath Assoc 66:303–307

    Google Scholar 

  13. Hechtman P (1977) Characterization of an activating factor required for hydrolysis of GM2-ganglioside catalyzed by hexosaminidase. Can J Biochem 55:315–324

    Google Scholar 

  14. Ho MW, O'Brien JS (1971) Gaucher disease: Deficiency of “acid” β-glucosidase and reconstitution of enzyme activity in vitro. Proc Natl Acad Sci USA 68:2810–2813

    Google Scholar 

  15. Juif JG, Luckel JC, Nussbaum JL, Stoebner R, Kapps R (1973) La ganglioside GM2 avec deficit complet en β-N-acetylhexosaminidase ou maladie de Sandhoff. Arch Franc Péd 30:29–43

    Google Scholar 

  16. Klibansky C, Saifer A, Feldman NI, Schneck L, Volk BV (1970) Cerebral lipids in a case of systemic GM2-gangliosidosis of a late infantile type. J Neurochem 17:339–346

    Google Scholar 

  17. Kolodny EH, Wald I, Moser HW, Cogan DG, Kuwabara T (1973) GM2-gangliosidosis without deficiency in the artificial substrate cleaving activity of hexosaminidases A and B. [Abstr]. Neurology (Minneap) 23:427

    Google Scholar 

  18. Korey SR, Terry RD (1963) Studies in Tay-Sachs disease. I. B. Clinical and pathological descriptions. J Neuropathol Exp Neurol 22:10–17

    Google Scholar 

  19. Li SC, Li YT (1976) An activator stimulating the enzymic hydrolysis of sphingoglycolipids. J Biol Chem 254:1159–1163

    Google Scholar 

  20. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  21. Marinetti GV, Erbland J, Stotz E (1959) The quantitative analysis of plasmalogens by paper chromatography. Biochim Biophys Acta 31:251–252

    Google Scholar 

  22. Menkes JH, O'Brien JS, Okada S, Grippo J, Andrews JM, Cancilla PA (1971) Juvenile GM2-gangliosidosis. Biochemical and ultrastructural studies on a new variation of Tay-Sachs disease. Arch Neurol 25:14–22

    Google Scholar 

  23. Miettinen T, Takki-Luukkainen IT (1959) Use of butyl acetate in determination of sialic acid. Acta Chem Scand 13:856–858

    Google Scholar 

  24. Norton WT, Autilio LA (1965) The chemical composition of bovine CNS myelin. Ann NY Acad Sci 122:77–85

    Google Scholar 

  25. Norton WT, Autilio LA (1966) The lipid composition of purified bovine brain myelin. J Neurochem 13:213–222

    Google Scholar 

  26. O'Neill B, Butler AB, Young E, Falk PM, Bass N (1978) Adultonset GM2-gangliosidosis, seizures, dementia, and normal pressure hydrocephalus associated with glycolipid storage in the brain and arachnoid granulation. Neurology (Minneap) 28: 1117–1123

    Google Scholar 

  27. Pilz H, Müller D, Sandhoff K, ter Meulen V (1968) Tay-Sachs'sche Krankheit mit Hexosaminidase-Defekt. Dtsch Med Wochenschr 39:1833–1839

    Google Scholar 

  28. Purpura DP (1978) Ectopic dendritic growth in mature pyramidal neurones in human ganglioside storage disease. Nature 276:520–521

    Google Scholar 

  29. Purpura DP, Suzuki K (1976) Distortion of neuronal geometry and formation of aberrant synapses in neuronal storage disease. Brain Res 116:1–21

    Google Scholar 

  30. Rapin I, Suzuki K, Suzuki K, Valsamis MP (1976) Adult (chronic) GM2-gangliosidosis. Arch Neurol 33:120–130

    Google Scholar 

  31. Sandhoff K, Andreae U, Jatzkewitz H (1968) Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs. Life Sci 7:283–288

    Google Scholar 

  32. Sandhoff K, Harzer K, Wässle N, Jatzkewitz H (1971) Enzyme alterations and lipid storage in three variants of Tay-Sachs disease. J Neurochem 18:2469–2489

    Google Scholar 

  33. Sandhoff K, Jatzkewitz H (1972) The chemical pathology of Tay-Sachs disease. In: Volk BW, Aronson SM (eds) Sphingolipids, sphingolipidoses, and allied disorders. Plenum Press, New York, pp 305–319

    Google Scholar 

  34. Searcy RL, Bergquist LM (1960) A new color reaction for the quantitation of serum cholesterol. Clin Chim Acta 5:192–199

    Google Scholar 

  35. Suzuki K (1964) A simple and accurate micromethod for quantitative determination of ganglioside patterns. Life Sci 3:1227–1233

    Google Scholar 

  36. Suzuki K (1967) Ganglioside patterns of normal and pathological brains. In: Aronson SM, Volk BW (eds) Inborn disorders of sphingolipid metabolism. Pergamon Press, Oxford, pp 215–230

    Google Scholar 

  37. Suzuki K (1978) Enzymatic diagnosis of sphingolipidoses. In: Ginsburg V (ed) Methods in enzymology, vol 50, part C. Academic Press, New York, pp 456–488

    Google Scholar 

  38. Suzuki K, Suzuki K, Kamoshita S (1969) Chemical pathology of GM1-gangliosidosis (generalized gangliosidosis). J Neuropathol Exp Neurol 28:25–73

    Google Scholar 

  39. Suzuki K, Suzuki K, Rapin I, Suzuki Y, Ishii N (1970) Juvenile GM2-gangliosidosis, Clinical variant of Tay-Sachs disease or a new disease. Neurology (Minneap) 20:190–204

    Google Scholar 

  40. Suzuki Y, Jacob K, Suzuki K, Kutty KM, Suzuki K (1971) GM2-gangliosidosis with total hexosaminidase deficiency. Neurology (Minneap) 21:313–328

    Google Scholar 

  41. Svennerholm L (1956) Quantitative estimation of cerebroside in nervous tissue. J Neurochem 1:42–53

    Google Scholar 

  42. Svennerholm L (1957) Quantitative estimation of sialic acids II. Colorimetric resorcinol hydrochloric acid method. Biochim Biophys Acta 24:604–611

    Google Scholar 

  43. Svennerholm L (1963) Chromatographic separation of human brain gangliosides. J Neurochem 10:612–623

    Google Scholar 

  44. Terry RD, Weiss M (1963) Studies in Tay-Sachs disease. II. Ultrastructure of the cerebrum. J Neuropathol Exp Neurol 22:18–55

    Google Scholar 

  45. Vidailhet M, Neimann N, Grignon G, Hartemann, P, Philippart M, Paysant P, Nabet P, Floquet J (1973) Maladie de Sandhoff (gangliosidose a GM2, de type 2). Arch Franc Péd 30:45–60

    Google Scholar 

  46. Volk BW, Adachi M, Schneck L, Saifer A, Kleinberg W (1969) G5-ganglioside variant of systemic late infantile lipidosis. Arch Path 87:393–403

    Google Scholar 

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This work was supported by NIH grants NS 03356, NS 10803, NS 10885, HD 01799, and NS 07098

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Goldman, J.E., Yamanaka, T., Rapin, I. et al. The AB-variant of GM2-gangliosidosis. Acta Neuropathol 52, 189–202 (1980). https://doi.org/10.1007/BF00705807

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