ABSTRACT
Mucolipidosis II and III reflect multiple deficiencies of many lysosomal hydrolases that require post-translational processing to form the recognition site that permits their cellular uptake. The fundamental defect is in N-acetylglucosaminyll-phosphotransferase (GlcNAc phosphotransferase) [1] (Figure 84.2, p. 554). The lysosomal enzyme substrates for this enzyme are glycoproteins containing reactive mannose molecules and in the reaction a GlcNAc phosphate is linked to the mannose; a subsequent phosphodiesterase reaction cleaves off the GlcNAc, leaving the mannose phosphate recognition site. Patients with I-cell disease, or mucolipidosis II, have complete deficiency of this enzyme, while patients with mucolipidosis III have varying amounts of residual activity of the enzyme. Variable patterns of clinical phenotype in mucolipidosis III reflect the considerable variation in enzyme activity as well as its effect on so very many lysosomal enzymes. The extent of the phenotypic variability has doubtless not yet been defined.
