Fucosidosis is an autosomal recessive lysosomal storage disease due to a deficiency of alpha-L-fucosidase activity in tissues and body fluids. Exponentially growing lymphoid cell cultures from four fucosidosis patients had 2.7-fold to 15.6-fold less extracellular alpha-L-fucosidase protein and 28.8-fold to 144.0-fold less intracellular alpha-L-fucosidase protein with negligible catalytic activity, compared to the mean of 19 control cultures. The percentage of total alpha-L-fucosidase protein released extracellularly by cultures from the four patients was 64 to 85%, compared to 35 +/- 9% for control cultures. Intracellular and extracellular enzyme forms in fucosidosis and control cell lines were glycoproteins containing polypeptide chains of Mr = 52,000. During a 1.5-hr pulse-label with 35S-methionine, alpha-L-fucosidase was synthesized by control cells and two fucosidosis cell lines as an intracellular form with Mr = 58,000. During a subsequent 21-hr chase with unlabeled methionine, mutant enzyme was almost entirely processed to an extracellular form with Mr = 62,000. In contrast, only 25-30% of control enzyme was processed to an extracellular form (Mr = 62,000), with the remainder retained intracellularly (Mr = 60,000). In the other two fucosidosis cell lines, alpha-L-fucosidase was synthesized as an intracellular form with Mr = 56,000 that was processed to an extracellular form with Mr = 60,000. In summary, the fucosidosis mutation(s) affected the catalytic activity, quantity, and extracellular release of alpha-L-fucosidase as expressed by lymphoid cells.
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