G(M1)-gangliosidosis in a cross-bred dog confirmed by detection of G(M1)-ganglioside using electrospray ionisation-tandem mass spectrometry

The post-mortem diagnosis of lysosomal storage diseases can be confounded b y the unavailability of suitable material. Here we report the diagnosis of G(M1)-gangliosidosis in a cross-bred dog, from which only formalin-fixed br ain was available, by a combination of electron microscopy and the detectio n of elevated levels of G(M1)-ganglioside within the tissue using the novel technique of electrospray ionisation tandem mass spectrometry. Electron mi croscopic examination of ultrathin sections of resin-embedded tissue reveal ed cytoplasmic inclusions (membranous cytoplasmic and zebra bodies) in brai n stem and cerebellar neurons that were characteristic of a gangliosidosis. Glycolipids were extracted from the fixed tissue and analysed by tandem ma ss spectrometry. Two major ions were detected, which corresponded to G(M1) (d18:1-C18:0) and G(M1) (d20:1-C18:0). Their identity was confirmed by comp arison of their fragmentation patterns with those of authentic standards. T he concentration of G(M1) was approximately sixfold higher on a wet weight basis than in the brain of a normal control dog, confirming the diagnosis o f G(M1)-gangliosidosis.