Stored dolichyl pyrophosphoryl oligosaccharides in Batten disease

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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 Man5–7GlcNAc2 and Glc3Man7GlcNAc2. In IB, they range from Man6–9GlcNAc2, 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.