Abstract
The availability of specific antibodies and cDNA probes for lysosomal hydrolases has revealed unexpected heterogeneity among the human inherited lysosomal storage diseases. Using α-fucosidase andN-acetyl-β-D-hexosaminidase deficiency variants as examples, it has been determined that a lysosomal hydrolase deficiency can result from DNA deletion mutations, failure to synthesize mRNA because of defective splicing, posttranslational defects in assembly, and synthesis of a precursor enzyme that is prematurely proteolytically degraded through lack of a protective protein. In some cases (fucosidosis), the different genotypes cannot be distinguished phenotypically, whereas in others (β-hexosaminidoses) the phenotypes can range from infantile neurodegeneration through juvenile motor neuron disease to adult neurodysfunction. Biochemical studies on both diseases have revealed several distinct genotypes. We show that some forms of fucosidosis result from unstable enzyme that can be stabilized by protease inhibitors, whereas partial β-hexosaminidase deficiences cannot be corrected by these protease inhibitors.
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Dawson, G., Johnson, K., McCabe, N.R. et al. Molecular heterogeneity in lysosomal storage diseases. Neurochemical Pathology 8, 203–217 (1988). https://doi.org/10.1007/BF03160147
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DOI: https://doi.org/10.1007/BF03160147