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-acetylglucosaminyl-l-phosphotransferase. Adenoassociated virus 8 mediated expression of N-acetylglucosamine-1-phosphotransferase attenuated bone loss in a mouse model of mucolipidoses II. A recombinant adeno-associated viral vector was found to increase bone density significantly in a knockout mouse model. Inclusions or vacuolation may be seen in other cells, such as biopsied cornea, bone marrow cells, or lymphocytes. Activities of the same enzymes are high in the media in which the cells are grown, which suggested at first that the cells were leaky. Mucolipidosis II/III shares many of the clinical manifestations of the classic mucopolysaccharidoses. 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.