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 result in the neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (INCL). Reduced palmitoyl-protein thioesterase enzyme has been 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 fibroblasts; (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 data establish that PPT is transported to lysosomes via the lysosomal enzyme:lysosomal enzyme receptor phosphomannosyl recognition system under normal physiological conditions and provide the basis for a useful clinical assay for INCL.