Abstract
Summary: Extensive clinical heterogeneity is seen in lysosomal storage disorders, regarding the age of onset and severity of symptoms, the organs involved, and effects on the central nervous system. A broad phenotypic spectrum is seen, for example, in mucopolysaccharidosis type I (Hurler/Scheie disease), Gaucher disease, the severalforms of GM2-gangliosidosis and the different manifestations of β-galactosidasedeficiency (GM1-gangliosidosis and Morquio disease type B). Variable clinical expression of the same enzyme defect is not well understood. The presence of different mutations is only part of the explanation, as intrafamilial variability is observed in many cases. Other mechanisms, for example the effect of specific activators, may also have an influence on phenotype.
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REFERENCES
Amaral O, Fortuna AM, Lacerda L, et al (1994) Molecular characterisation of type 1 Gaucher disease families and patients: intrafamilial heterogeneity at the clinical level. J Med Genet 31: 401–404.
Beck M, Glössl J, Grubisic A, et al (1986) Heterogeneity of Morquio disease. Clin Genet 29: 325–331.
Beck M, Petersen EM, Spranger J, et al (1987) Morquio's disease type B (beta-galactosidase deficiency) in three siblings. S Afr Med J 72: 704–707.
Beck M, Barone R, Hoffmann R, et al (1995) Inter-and intrafamilial variability in mucolipidosis II (I-cell disease). Clin Genet 47: 191–199.
Bunge S, Clements PR, Byers S, et al (1998) Genotype-phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies. Biochim Biophys Acta 1407: 249–256.
Conzelmann E, Sandhoff K (1983/ 1984) Partial enzyme deficiencies: residual activities and the development of neurological disorders. Dev Neurosci 6: 58–71.
d'Azzo A, Proia RL, Kolodny EH, et al (1984) Faulty association of alpha-and beta-subunits in some forms of beta-hexosaminidase A deficiency. J Biol Chem 259: 11070–11074.
Holzgreve W, Grobe H, von Figura K, et al (1981) Morquio syndrome: clinical findings in 11 patients with MPS IVA and 2 patients with MPS IVB. Hum Genet 57: 360–365.
Leinekugel P, Michel S, Conzelmann E, et al (1992) Quantitative correlation between the residual activity of β-hexosaminidase A and arylsulfatase A and the severity of the resulting lysosomal storage disease. Hum Genet 88: 513–523.
McDowell GA, Cowan TM, Blitzer MG, et al (1993) Intrafamilial variability in Hurler syndrome and Sanfilippo syndrome type A: implications for evaluation of new therapies. Am J Med Genet 47: 1092–1095.
Meier EM, Schwarzmann G, Fürst W, et al (1991) The human GM2 activator protein. A substrate specific cofactor of ®-hexosaminidase A. J Biol Chem 266: 1879–1887.
Paschke E, Kresse H (1982) Morquio disease, type B: activation of GM1-®-galactosidase by GM1-activator protein. Biochem Biophys Res Commun 109: 568–575.
Patterson MC, Horowitz M, Abel RB, et al (1993) Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvement in Gaucher's disease. Neurology 43: 1993–1997.
Redonnet-Vernhet I, Ploos van Amstel JK, Jansen RP, et al (1996) Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene. J Med Genet 33: 682–688.
Sa Miranda MC, Aerts JM, Pinto R, et al (1990) Activity of glucocerebrosidase in extracts of different cell types from type 1 Gaucher disease patients. Clin Genet 38: 218–227.
Tayebi N, Stone DL, Sidransky E (1999) Type 2 Gaucher disease: an expanding phenotype. Mol Genet Metab 68: 209–219.
Willems PJ, Gatti R, Darby JK, et al (1991) Fucosidosis revisited: a review of 77 patients. Am J Med Genet 38: 111–131.
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Beck, M. Variable clinical presentation in lysosomal storage disorders. J Inherit Metab Dis 24 (Suppl 2), 47–51 (2001). https://doi.org/10.1023/A:1012463605992
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DOI: https://doi.org/10.1023/A:1012463605992