Abstract
Extract: A marked intracellular reduction of six lysosomal enzymes could be demonstrated in fibroblasts from four different patients with mucolipidosis type II or I-cell disease. In contrast to that finding, conditioned media from the same cells contained a 2—10-fold increase of the activities of five lysosomal enzymes over control values. In obligate heterozygotes elevated lysosomal enzyme activities in the conditioned media were also found, but normal enzyme activities were measured intracellularly. A functional impairment of the lysosomal degradation of (35SO4) mucopolysaccharide (MPS) and of (35S)-sulfatide could be shown in the I-cell fibroblasts, as a consequence of decreased enzyme activities.
Substitution of the enzyme-deficient cells with normal urinary arylsulfatase A and with mucopolysaccharide degrading factors from normal conditioned media was possible, but failed when urine from patients or conditioned media factors from the I-cell fibroblasts were used.
Speculation: Genetic disorders of lysosomal functions can be caused not only by lack of synthesis or by a structural defect of a lysosomal enzyme, but also by a genetically determined loss of enzyme into the extracellular fluid. These lysosomal enzymes are functionally abnormal only insofar as they cannot be retained within the cells, and, furthermore, once they are outside of the cells, they can not re-enter the cells by pinocytosis as can normal enzymes.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wiesmann, U., Herschkowitz, N. Studies on the Pathogenetic Mechanism of I-Cell Disease in Cultured Fibroblasts. Pediatr Res 8, 865–870 (1974). https://doi.org/10.1203/00006450-197411000-00002
Issue Date:
DOI: https://doi.org/10.1203/00006450-197411000-00002
Keywords
This article is cited by
-
Chromatographic components of β-hexosaminidase in I-cell disease (Mucolipidosis II)
Human Genetics (1979)
-
Correction of human mucolipidosis II enzyme abnormalities in somatic cell hybrids
Nature (1977)
-
Serum hexosaminidase activity in I-cell disease carriers
Human Genetics (1977)
-
Prenatal diagnosis of mucolipidosis II (I-cell disease)
European Journal of Pediatrics (1976)
-
Prenatal diagnosis of I-cell disease
Humangenetik (1975)