Oligosaccharyl diphosphodolichols in the ceroid-lipofuscinoses.

Autopsy brain samples from patients with late-infantile, juvenile and adult forms of ceroid-lipofuscinosis (CL) and cultured skin fibroblasts from juvenile CL were analyzed for the content of phosphodolichol (P-Dol) related compounds. The levels of P-Dol obtained on treatment with hot dilute acid of the chloroform-methanol (CM 2:1) extract and the chloroform-methanol-water (CMW 1:1:3) extract of the residue were estimated by high performance liquid chromatography. Compared to age-matched control individuals, the levels of P-Dol obtained in both the extracts were increased more than 6.6 times in all the patient samples. Further analysis of the CMW extract indicates that the increased P-Dol is primarily due to oligosaccharyl diphosphodolichol. Cultured skin fibroblasts from the juvenile form of CL show normal level of free dolichol and elevated level of phosphorylated dolichols. Glycoprotein synthesis measured by incorporation of labeled glucosamine show no deficit in the transfer of oligosaccharides from lipids to proteins. A hypothesis is presented to explain the accumulation of oligosaccharyl diphosphodolichol and deficiency of lysosomal proteases in ceroid-lipofuscinosis.