Stored dolichyl pyrophosphoryl oligosaccharides in Batten disease

Abstract

Each of the 3 childhood forms of Batten disease, juvenile (JB), late-infantile (LIB), and infantile (IB), have abnormally high brain concentrations of dolichyl pyrophosphoryl oligosaccharides (Dol-PP-OS). In this study, the carbohydrate portions of Dol-PP-OS were analysed: in JB and LIB, they range in size from Man₂GlcNAc₂ to Glc₃Man₉GlcNAc₂, predominant components being Man_5–7GlcNAc₂ and Glc₃Man₇GlcNAc₂. In IB, they range from Man_6–9GlcNAc₂, no glucose containing oli-gosacchsrides being identified. In Batten disease, the main subcellular location of Dol-PP-OS is within storage material, where it represents up to 7% of the dry weight. [³H]-Mannose incorporation experiments with cultured fibroblasts show that synthesis of Dol-PP-OS in JB is normal. We infer that the glycosyla-tion intermediate Glc₃Man₉GlcNAc₂-PP-dol-ichol is synthesised normally within the endo-plasmic reticulum in Batten disease, but that catabolic derivatives accumulate within the lysosomes. It is unclear whether this process is central to the pathogenesis of the disease, though in IB a defect in the release of man-nose residues from Dol-PP-OS is a distinct possibility.