Increased Concentration of G M1 -Ganglioside in Cerebrospinal Fluid in Dogs with G M1 - and G M2 -Gangliosidoses and its Clinical Application for Diagnosis

Abstract

G_M1- and G_M2-gangliosidoses are lethal lysosomal diseases that are caused by a defect of acid hydrolases, resulting in the intralysosomal accumulation of the specific physiological substrates, G_M1- and G_M2-gangliosides, respectively. In the present study a method for the diagnosis of canine G_M1-gangliosidosis was established using canine cerebrospinal fluid (CSF). The concentration of G_M1-ganglioside in CSF was determined by thin-layer chromatography–enzyme immunostaining using biotin-conjugated cholera toxin B, which specifically binds with G_M1-ganglioside. The concentration of CSF G_M1-ganglioside was increased in Shiba dogs with G_M1-gangliosidosis, and the increased level was approximately proportional to the age of the dogs. The concentration was high in the affected dog even at 5 months of age, when Shiba dogs with G_M1-gangliosidosis first manifest neurologic signs. In addition, the concentration of CSF G_M1-ganglioside in a dog with the G_M2-gangliosidosis 0 variant (Sandhoff disease) was also 7 times the normal level. From these results it was concluded that this laboratory technique enables a definitive and early diagnosis of canine G_M1-gangliosidosis even if tissues and organs cannot be obtained. However, because G_M1-ganglioside can also be elevated in cases of G_M2-gangliosidosis, it is necessary to assay for specific enzyme deficiencies to definitively separate G_M1- from G_M2-gangliosidosis.

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