Naturally occurring G_M2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical Tay-Sachs disease (type B G_M2 gangliosidosis)

Abstract

Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of depression, ataxia, circling and visual deficits were studied. Cerebrospinal fluid analyses revealed vacuolated macrophages that contained long parallel needle-like intracytoplasmic inclusions. Light microscopically, nerve cell bodies throughout the brain, ganglion cells within the retina and neurons in the myenteric plexuses were variably swollen and had pale granular to finely vacuolated eosinophilic cytoplasm. Neuronal cytoplasm stained specifically with sudan black and Luxol-fast blue stains. Within the brain there were occasional axonal spheroids, foci of astrogliosis and scattered microglial cells with abundant pale foamy cytoplasm. Electron microscopy of the brain and retina revealed numerous neurons and ganglion cells, respectively, with multiple membrane-bound structures that contained compact electron-dense membranous whorls and fewer parallel membranous stacks. Thin layer chromatography of total lipid extracts of the cerebral cortex of both cases revealed massive accumulation of G_M2 ganglioside. Crude kidney extracts of the two affected deer were able to hydrolyze 4-methylumbelliferyl β-GlcNAc, but not 4-methylumbelliferyl β-GlcNAc-6-sulfate, indicating the defect of β-hexosaminidase A. Cellogel electrophoresis of the kidney extracts also revealed the deficiency of β-hexosaminidase A in the two deer. It is concluded that these two deer had the biochemical lesion identical to that of human type B G_M2 gangliosidosis (classical Tay-Sachs disease).