I-Cell Disease

Abstract

The I-cell disease (mucolipidosis II) is a lysosomal storage disease, inherited in an autosomal recessivemanner. The defect lies in the biosynthesis of the mannose 6phosphate recognition marker for the targeting of lysosomal enzymes into lysosomes. The effect is therefore most far reaching since it affects all lysosomal enzymes. Specifically, the N-acetylglucosaminyl-1-phosphotransferase, which catalyses the first step in the synthesis of mannose 6-phosphate (cf. Fig. 53), is defective. The lack of the recognition marker on de novo synthesised lysosomal enzymes results in their secretion into the extracellular space. The detection of elevated serum concentrations of multiple lysosomal enzymes is therefore diagnostic. Clinically, I-cell disease is characterised by early onset and progressive severe psychomotoric retardation accompanied by skeletal abnormalities and coarse facial shape. Surprisingly, not all body cells are devoid of lysosomal enzymes, although they are all lacking phosphotransferase. This indicates that certain cells such as hepatocytes, Kupffer cells, and leukocytes are able to endocytose lysosomal enzymes through an unknown alternate, mannose 6-phosphate-independent mechanism.