PALMITOYL-PROTEIN THIOESTERASE DEFICIENCY IN FIBROBLASTS OF INDIVIDUALS WITH INFANTILE NEURONAL CEROID-LIPOFUSCINOSIS AND I-CELL DISEASE

Mutations in the gene encoding a recently described lysosomal enzyme, palmitoyl-protein thioesterase (PPT), have recently been shown to resu lt in the neurodegenerative disorder, infantile neuronal ceroid lipofu scinosis (INCL). Reduced palmitoyl-protein thioesterase enzyme has bee n demonstrated previously in INCL brain and immortalized lymphoblasts. In the current paper, we demonstrate that: (1) PPT can be detected by immunoblotting and enzyme activity assays in normal human skin fibrob lasts; (2) INCL fibroblasts are deficient in PPT activity; (3) I-cell disease fibroblasts show markedly reduced intracellular levels of PPT but markedly increased levels of PPT in cell culture medium. These dat a establish that PPT is transported to lysosomes via the lysosomal enz yme:lysosomal enzyme receptor phosphomannosyl recognition system under normal physiological conditions and provide the basis for a useful cl inical assay for INCL.