Stored dolichyl pyrophosphoryl oligosaccharides in Batten disease

✍ Scribed by Hall, Nicholas A. ;Thomas-Oates, Jane E. ;Dell, Anne ;Haltia, Matti ;Lake, Brian D. ;Patrick, A. Desmond

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 602 KB
• Volume: 42
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320420431

✦ Synopsis

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-0s). In this study, the carbohydrate portions of Dol-PP-OS were analysed: in J B and LIB, they range in size from Man,GlcNAc, to Glc3ManeGlcNAc,, predominant components being Man,,GlcNAc, and Glc,Man7GlcNAcz. In IB, they range from MQ-,GlcNAc,, no glucose containing oligosaccharides being identified. In Batten disease, the main subcellular location of Dol-PP-0s is within storage material, where it represents up to 7% of the dry weight. [3Hl-Mannose incorporation experiments with cultured fibroblasts show that synthesis of Dol-PP-OS in J B is normal. We infer that the glycosylation intermediate Glc3ManeGlcNAc,-PP-dolichol is synthesised normally within the endoplasmic 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 mannose residues from Dol-PP-OS is a distinct possibility.