Abnormal lysosomal hydrolases excreted by cultured fibroblasts in I-cell disease (mucolipidosis II)

The isozymes of β-D-N-acetylhexosaminidase excreted by cultured skin fibroblasts derived from patients with I-cell disease (ICD) differ electrophoretically from the isozymes excreted by fibroblasts from normal individuals and from the intracellular isozymes of both cell types. The higher electronegative charge at pH 6 presumably results from sialic acid residues not present on normal and ICD intracellular enzyme or on normal fibroblast-excreted enzyme, since neuraminidase treatment only affects the mobility of the ICD fibroblast-excreted enzyme. A higher electronegative charge than that of normal fibroblast-excreted or intracellular enzymes has also been detected in ICD fibroblast-excreted arylsulfatase, β-glucuronidase and α-L-fucosidase. Additional sialic acid residues on the ICD-excreted hydrolases may result from abnormal exocytosis, and may be responsible for the inability of these enzymes to enter normal or ICD fibroblasts by adsorptive pinocytosis.