G_M1-gangliosidosis Types 1 and 2: Enzymatic Differences in Cultured Fibroblasts

Abstract

${\text{G}}_{{\text{M}}_{\text{1}}}$-GANGLIOSIDOSIS occurs in two clinical forms^1,2. Type 1 resembles Hurler's syndrome somatically, but its psychomotor aspect is apparent from birth and progresses rapidly to cause death by 2 years of age. Type 2 presents no Hurler signs and its psychomotor course, though similar to that in type 1, is neither congenital nor is rapidly progressive; death occurs about 5 years of age. In addition to the accumulation of ${\text{G}}_{{\text{M}}_{\text{1}}}$-ganglioside in neural, and to a lesser extent in extraneural, tissues both types share a profound, generalized deficiency of lysosomal β-galactosidase, with storage and excretion of modified keratin sulphates. Although the clinical and biochemical definition of the type 2 form is very recent³, failure to observe both clinical types within single sibships is sufficient to suggest that each is caused by a different mutant gene. To test this hypothesis we have examined the gangliosides, glycos-aminoglycans and residual β-galactosidase activities in fibroblast cell strains derived from skin in the deltoid area of patients with each type of ${\text{G}}_{{\text{M}}_{\text{1}}}$-gangliosidosis. This communication deals only with the last focus of interest.