DIFFERENTIATION OF TYPES 1, 2 and 3 GM1-GANGLIOSIDOSIS IN SKIN FIBROBLAST CULTURE

Abstract

Type 1 GM1-gangliosidosis presents in early infancy with a pseudo-Hurler phenotype. Type 2 begins about 1 year of age with neural but little or no skeletal involvement and no visceromegaly. β-galactosidase (β-gal) activities were measured with the 4-methylumbelliferyl substrate in strains from two type 1 and four type 2 patients. In normal strains, pH optimum is 4.4 and 95% of original activity is destroyed after 2 min at 55°C. A minor component is very heat stable and has greater activity at pH 3.8 than 4.4. In type 1 strains, residual β-gal activity is less than 1% of normal, has a pH optimum around 3.7 and is very thermostable. In type 2 strains, residual activity is about 3% of normal, has a pH optimum around 4.4 and its. thermostability profile is biphasic, the larger component representing the major heat-labile species of β-gal in normal strains. One of our type 2 strains was derived from a patient whose liver β-gal had a pH optimum around 6.5 with the p-nitrophenyl substrate. Another was from a patient whose liver β-gal had a similar pH optimum with the 4-methylumbelliferyl substrate. Thus, the residual β-gal activity in type 2 is tissue-specific. The type 3 cell strain ia from a patient with a clinical course less severe than type 2. Its β-gal activity is several times greater than those of type 2 strains and it stains normally with the indigogenic histochemical substrate for β-gal.