G M1 -gangliosidosis in a cross-bred dog confirmed by detection of G M1 -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.

Recognition and Diagnosis of Lysosomal Storage Diseases in the Cat and Dog

“…In this case, the authors described the use of electrospray ionization-tandem mass spectrometry as a means of identifying glycolipids extracted from fixed tissue. 13 This investigation led to the confirmation of a diagnosis of G M1 gangliosidosis. Thus, the diagnosis of lysosomal storage diseases involves a sequential series of diagnostic procedures, often requiring increasing specialized expertise.…”

“…Frequently, however, many of the neuronal storage diseases begin with cerebellar or cerebellovestibular signs such as tremor, ataxia, dysmetria, and nystagmus with progression to paresis and paralysis. These signs are prevalent early in the clinical course for gangliosidoses in dogs and cats, [7][8][9][10][11][12][13] Niemann-Pick disease types A 23,24 and C 25,26,45 and globoid cell leukodystrophy, [19][20][21][22] canine Gaucher disease, 18 and feline ␣-mannosidosis. [2][3][4] Later, behavioral abnormalities and seizures may be seen, although these changes may also be found earlier in diseases such as globoid cell leukodystrophy in the Poodle, 21 fucosidosis, 1 and ceroid lipofuscinosis.…”

PS Dependent APP Cleavage Regulates Glucosylceramide Synthase and is Affected in Alzheimer's Disease

“…After desalting the lipids by a reversed-phase cartridge (Waters Oasis, Eschborn, Germany) according to Whitfield et al [44] the concentrated ganglioside extract was applied to silica gel thin-layer chromatography (TLC) plates (Merck, Darmstadt, Germany) and separated by using CHCl 3 : MeOH: H 2 O-CaCl 2 0.2% (60: 35: 8; v/v) as solvent system [45]. Gangliosides were visualized by iodine and identified by their Rf-values and available standards.…”

“…As gangliosides were consistently found to be associated with AD [44], we investigated in the present study a potential function of PS-dependent APP processing in the regulation of the ganglioside de novo synthesis.…”

Clinical and Clinico-Pathologic Characteristics of Shiba Dogs with a Deficiency of Lysosomal Acid .BETA.-Galactosidase: A Canine Model of Human GM1 Gangliosidosis.

“…Among the various models of GM1 gangliosidosis, the canine disease probably best resembles the human disease genetically, clinically, biochemically and pathologically [15]. In dogs, the disease has been described in mixed-breed beagles [9], English springer spaniels [2], Portuguese water dogs [11,12], Alaskan huskies [6,7], Shiba dogs [16,20] and a crossbred dog [18]. Molecular defects that cause the disease have been identified in Portuguese water dogs [17] and Shiba dogs [19].…”