Hostname: page-component-745bb68f8f-s22k5 Total loading time: 0 Render date: 2025-01-14T19:56:56.277Z Has data issue: false hasContentIssue false
  • English
  • Français

Lysosomal enzymes in ataxia: discovery of two new cases of late onset hexosaminidase A and B deficiency (adult sandhoff disease) in French Canadians

Published online by Cambridge University Press:  18 September 2015

A. Barbeau ,
L. Plasse ,
T. Cloutier ,
S. Paris  and
M. Roy
A. Barbeau*
Affiliation:
Clinical Research Institute of Montreal
L. Plasse
Affiliation:
Clinical Research Institute of Montreal
T. Cloutier
Affiliation:
Clinical Research Institute of Montreal
S. Paris
Affiliation:
Clinical Research Institute of Montreal
M. Roy
Affiliation:
Clinical Research Institute of Montreal
*
Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W IR7
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

We have measured in leukocytes the following lysosomal enzymes in II Friedreich disease cases, 11 “atypical” recessive ataxias, 13 neurological controls and 16 normal controls: hexosaminidase A and B; (3-galactosidase and neuraminidase (labile and cold stable, or A and B). The lysosomal enzyme deficiencies known to produce certain forms of spinocerebellar degeneration were not present in Friedreich's disease or the Charievoix-Saguenay syndrome. The very small scale survey of “atypical” recessive ataxias revealed 3 cases of severe deficiencies in hexosaminidase activity. Two adult brothers presenting with the clinical phenotype of Kugelberg-Welander disease (one also with ataxia), were shown to have a severe deficiency of both HEX A and HEX B activity (Sandhoff biochemical pattern). This is the first such report. A further adult female patient, unrelated to the others, had a severe isolated deficiency of HEX B and presented with a very slowly progressive and mild ataxia with severe internal strabismus. These patients and their families are being studied clinically and biochemically in greater detail and will be reported elsewhere. However these preliminary findings justify screening for such lysosomal defects in all cases of “atypical” recessive ataxia.

Type
C—Biochemistry
Information
Canadian Journal of Neurological Sciences , Volume 11 , Issue S4 , November 1984 , pp. 601 - 606
Copyright
Copyright © Canadian Neurological Sciences Federation 1984

References

Andermann, F, Andermann, E (1982) Neuroepidemiological studies in Eastern Canada-Genetic aggregates in specific population, includ-ing three newly described autosomal recessive syndromes. In: Fukuyama, Y (ed). Child Neurology, Excerpta Med Foundat ICS 579, pp 351–365.Google Scholar
Andermann, E, Scriver, CR, Wolfe, LS, Dansky, L, Andermann, F (1977) Genetic variants of Tay-Sachs disease: Tay-Sachs disease and SandhofTs disease in French Canadians, juvenile Tay-Sachs disease in Libanese Canadians, and a Tay-Sachs screening program in the French Canadian population. In: Kabak, MM, Rimoin, DL, O’Brien, JS (eds). Tay-Sachs disease: screening and prevention. New York, A.R. Liss, pp 161–188.Google Scholar
Aronson, SM (1964) Epidemiology. In: Volk, BW (ed). Tay-Sachs disease. New York, Grane and Stratton, pp 118–153.Google Scholar
Barbeau, A, Charbonneau, M, Cloutier, T (1980) Leukocyte glutamate dehydrogenase activity in various hereditary ataxias. Can J Neurol Sci 7: 421–424.CrossRefGoogle ScholarPubMed
Bouchard, JP, Barbeau, A, Bouchard, R, Bourchard, RW (1978) Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Can J Neurol Sci 5: 61–69.CrossRefGoogle ScholarPubMed
De Duve, C, Wattiaux, R (1966) Functions of lysosomes. Annual Rev Physiol 28: 435–492.CrossRefGoogle ScholarPubMed
Dreyfus, JC, Poenaru, L, Svennerholm, , (1975) Absence of Hexosaminidase A and B in a normal adult. New Engl J Med 292: 61–63.CrossRefGoogle Scholar
Federico, A, Cecio, A, Battani, GA, Michalski, JC, Strecker, G, Guassi, GC (1980) Macular cherry-red spot and myoclonus syndrome — juvenile form of sialidosis. J Neurol Sci 48: 157–169.CrossRefGoogle ScholarPubMed
Geoffroy, B, Barbeau, A, Breton, G, Lemieux, B, Aubé, M, Léger, C, Bouchard, JP (1976) Clinical description and roentgenologic evaluation of patients with Friedreich’s ataxia. Can J Neurol Sci 3:279–286.CrossRefGoogle ScholarPubMed
Gilbert, F, Kucherlapati, R, Creagan, RP, Murnana, MJ, Darlington, GJ, Ruddle, FH (1975) Tay-Sachs’ and Sandhoffs disease: the assignment of genes for Hexosaminidase A and B to individual human chromosomes. Proc Nat Acad Sci 72: 263–267.CrossRefGoogle Scholar
Goldie, WD, Holtzman, D, Suzuki, K (1977) Chronic Hexosaminidase A and B deficiency. Ann Neurol 2: 156–158.CrossRefGoogle Scholar
Hong, VN, Beauregard, G, Potier, M, Belisle, M, Mameli, L, Gatti, R, Durand, P (1980) Studies on sialidoses — Properties of human leuko-cyte neuraminidases. Biochem Biophys Acta 616: 259–270.Google ScholarPubMed
Johnson, WG (1981) The clinical spectrum of hexosaminidase deficiency diseases. Neurology (N.Y.) 31: 1453–1456.CrossRefGoogle ScholarPubMed
Johnson, WG (1982) Hexosaminidase deficiency: a cause of recessively inherited motor diseases. Adv Neurol 36: 159–164.Google Scholar
Johnson, WG, Chutorian, AM (1978) Inheritance of the enzyme defect in a new hexosaminidase deficiency disease. Ann Neurol 4: 399–403.CrossRefGoogle Scholar
Johnson, WG, Chutorian, A, Miranda, A (1977) A new juvenile hexosaminidase deficiency disease presenting as cerebellar ataxia. Neurology 27: 1012–1018.CrossRefGoogle ScholarPubMed
Johnson, WG, Cohen, CS, Miranda, AF, Waran, SP, Chutorian, AM (1980) α-locus hexosaminidase genetic compound with juvenile gangliosidosis phenotype: clinical, genetic, and biochemical studies. Am J Hum Genet 32: 508–518.Google ScholarPubMed
Johnson, WG, Wigger, HJ, Karp, HR, Glaubiger, LM, Rowland, LP (1982) Juvenile spinal muscular atrophy: a new hexosaminidase deficiency phenotype. Ann Neurol 2: 11–16.CrossRefGoogle Scholar
Kelly, TE, Reynolds, LW, O’Brien, JS (1976) Segregation within a family of two mutant alleles for hexosaminidase A. Clinical Genetics 9: 540–543.CrossRefGoogle ScholarPubMed
Kolodny, EH, Raghavan, SS (1983) GM2-gangliosidosis-Hexosaminidase mutations not of the Tay-Sachs type produce unusual clinical variants. Trends in Neurol Sci 6: 16–20.CrossRefGoogle Scholar
Kuriyama, M, Miyatake, T, Owada, M, Kitagawa, T (1982) Neuraminidase activities in sialidosis and mucolipidosis. J’Neurol Sci 54: 181–187.CrossRefGoogle ScholarPubMed
Kuriyama, M, Okada, S, Tanaka, Y, Umezaki, H (1980) Adult mucolipidosis with β-galactosidose and neuraminidase deficiencies. J Neurol Sci 46: 245–254.CrossRefGoogle Scholar
Lane, AB, Jenkins, T (1978) Two variant hexosaminidase β-chain alleles segregating ina South Africanfamily. Clin Chimica Acta 87:219–228.CrossRefGoogle Scholar
Lowden, JA, O’Brien, JS (1979) Sialidosis: a review of human neuraminidase deficiency. Am J Hum Genet. 31: 1–18.Google ScholarPubMed
Lowry, OH, Rosebrough, NJ, Farr, AL, Randall, RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 93: 265–275.CrossRefGoogle Scholar
Macleod, RM, Wood, S, Jan, JE, Applegarth, DA, Dolman, CL (1977) Progressive cerebellar ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10 year-old child: Juvenile Sandhoffs disease. Neurology 27: 571–573.CrossRefGoogle Scholar
Melancon, SB, Potier, M, Geoffroy, G, Dallaire, L (1974) Maladie de Sandhoff: étude clinique et génétique chez une enfant canadienne-française. Union Méd Can 103: 1218–1222.Google Scholar
Mueller, OT, Shows, TB (1982) Human β-galactosidase and α-neuraminidase deficient mucolipidosis: genetic complementation analysis of the neuraminidase deficiency. Hum Gent 60: 158–162.CrossRefGoogle ScholarPubMed
Musarella, MA, Raab, EL, Rudolph, SH, Grabowski, GA, Desnick, RJ (1982) Oculomotor abnormalities in chronic GM2 gangliosidosis. J Ped Ophth Strab 19: 80–89.CrossRefGoogle ScholarPubMed
Navon, R, Argov, Z, Brand, N, Sandbank, U (1981) Adult GM2 gangliosidosis in association with Tay-Sachs disease: a new phenotype. Neurology (NY) 31: 1397–1401.CrossRefGoogle ScholarPubMed
O’Brien, JS, Okada, S, Chen, A (1970) Tay-Sachs disease: detection of hétérozygotes and homozygotes by serum hexosaminidase assay. N Engl J Med 283: 15–20.CrossRefGoogle ScholarPubMed
O’Neill, B, Butler, AB, Young, E, Falk, PM, Bass, NH (1978) Adult-onset GM2 gangliosidosis — Seizures, dementia, and normal pressure hydrocephalus associated with glycolipid storage in the brain and arachnoid granulation. Neurology 28: 1117–1123.CrossRefGoogle ScholarPubMed
Oonk, JGW, van der Helm, HJ, Martin, JJ (1979) Spino-cerebellar degeneration: hexosaminidase A and B deficiency in two adult sisters. Neurology 29: 380–384.CrossRefGoogle Scholar
Philippart, M (1978) Clinical and biochemical pathophysiology of ataxia in the sphingolipidoses. Adv Neurol 21: 131–149.Google ScholarPubMed
Rapin, I, Suzuki, K, Suzuki, , Valsamis, MP (1976) Adult (chronic) GM2 gangliosidosis – atypical spinocerebellar generation in a Jewish sibship. Arch Neurol 33: 120–130.CrossRefGoogle Scholar
Robinson, D, Stirling, JL (1968) N-acetylβ-glucosaminidases in human spleen. Biochem J 107: 321–327.CrossRefGoogle ScholarPubMed
Sakuraba, H, Suzuki, Y, Akagi, M, Sakai, M, Amano, N (1983) β-galactosidase — neuraminidase deficiency (galactosialidosis): clinical, pathological, and enzymatic studies in a postmortem case. Ann Neurol 13: 497–503.CrossRefGoogle Scholar
Sandhoff, K, Andreae, Y, 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.CrossRefGoogle Scholar
Snyder, R, Brady, RO (1969) The use of white cells as a source of diagnostic material for lipid storage diseases. Clin Chim Acta 25: 331–338.CrossRefGoogle ScholarPubMed
Suzuki, Y, Berman, PH, Suzuki, K (1971) Detection of Tay-Sachs disease hétérozygotes by assay of hexosaminidase A in serum and leukocytes. J Pediatr 78: 643–647.CrossRefGoogle ScholarPubMed
Suzuki, Y, Sakuraba, H, Potier, M, Akagi, M, Sakai, M, Beppu, H (1981) β-galactosidase-neuraminidase deficiency in adults: deficiency of a freeze-labile neuraminidase in leukocytes and fibroblasts. Hum Genet 58: 387–389.CrossRefGoogle ScholarPubMed
Tsuji, S, Yamada, T, Ariga, T, Toyoshina, I, Yamaguchi, H, Kitahara, Y, Miyatake, T, Yamakawa, T (1984) Carrier detection of sialidosis with partial β-galactosidase deficiency by the assay of lysosomal sialidase in lymphocytes. Ann Neurol 15: 181–183.CrossRefGoogle ScholarPubMed
Tsuji, S, Yamada, T, Tsutsumi, A, Miyatake, T (1982) Neuraminidase deficiency and accumulation of sialic acid in lymphocytes in adult type sialidosis with partial β-galactosidase deficiency. Ann Neurol 11: 541–543.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
Willner, JP, Grabowski, GB, Gordon, RE, Bender, AN, Desnick, RJ (1981) Chronic GM2 gangliosidosis masquerading as atypical Friedreich’s ataxia: clinical,morphologic, and biochemical studies of nine cases. Neurology (NY) 31: 787–798.CrossRefGoogle ScholarPubMed
Wood, S, MacDougall, BG (1976) Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts. Am J Hum Genet 28: 489–495.Google ScholarPubMed
Yamada, T, Tsuji, S, Ariga, T, Miyatake, T (1983) Lysosomal sialidase deficiency in sialidosis with partial β-galactosidase deficiency. Biochim Biophys Acta 755: 106–111.CrossRefGoogle ScholarPubMed
Yamaguchi, H, Okamoto, K, Shooji, M (1983) A case of adult type sialidosis with partial β-galactosidase deficiency without myoclonus. Clin. Neurol. 23: 1–8.Google ScholarPubMed