title: GM1-gangliosidosis in a cross-bred dog confirmed by detection of GM1-ganglioside using electrospray ionisation-tandem mass spectrometry.
abstract: The post-mortem diagnosis of lysosomal storage diseases can be confounded by the unavailability of suitable material. Here we report the diagnosis of GM1-gangliosidosis in a cross-bred dog, from which only formalin-fixed brain was available, by a combination of electron microscopy and the detection of elevated levels of GM1-ganglioside within the tissue using the novel technique of electrospray ionisation tandem mass spectrometry. Electron microscopic examination of ultrathin sections of resin-embedded tissue revealed cytoplasmic inclusions (membranous cytoplasmic and zebra bodies) in brain stem and cerebellar neurons that were characteristic of a gangliosidosis. Glycolipids were extracted from the fixed tissue and analysed by tandem mass spectrometry. Two major ions were detected, which corresponded to GM1 (d18:1-C18:0) and Gm1 (d20:1-C18:0). Their identity was confirmed by comparison of their fragmentation patterns with those of authentic standards. The concentration of GM1 was approximately sixfold higher on a wet weight basis than in the brain of a normal control dog, confirming the diagnosis of GM1-gangliosidosis.
authors.affiliation: Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Whitfield
authors.forename: A W
authors.initials: AW
authors.lastname: Johnson
authors.forename: K A
authors.initials: KA
authors.lastname: Dunn
authors.forename: A J
authors.initials: AJ
authors.lastname: Delauche
authors.forename: B G
authors.initials: BG
authors.lastname: Winchester
authors.forename: R J
authors.initials: RJ
authors.lastname: Franklin
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D004283:Dog Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005677:G(M1) Ganglioside / Q000032:analysis*; D016537:Gangliosidosis, GM1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D006017:Glycolipids / Q000032:analysis; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D006017:Glycolipids; D005677:G(M1) Ganglioside