Prenatal lesions in an ovine fetus with GM₁ gangliosidosis

Abstract

Sheep affected with ovine GM1 gangliosidosis are normal at birth and develop clinical signs, initially ataxia, commencing at approximately 5 months of age, which progresses rapidly to recumbency. Superovulation and embryo transfer techniques were applied to a flock of carrier sheep of ovine GM1 gangliosidosis to increase the numbers of carrier and affected animals. A recipient ewe with 3 at-risk fetuses died at 4 months of gestation (normal ovine gestation is 5 months), and spectrofluorimetric assay of cerebral lysosomal beta-galactosidase of the fetuses showed that 2 were carriers and one was an affected fetus. The affected fetus had marked cytoplasmic enlargement and vacuolization of central and peripheral nervous system neuronal soma and of hepatocytes and renal epithelial cells. Lectin histochemistry indicated abnormal storage of complex carbohydrates, with terminal saccharide moieties consisting of beta-galactose, N-acetylneuraminic acid, and N-acetylgalactosamine. This case underlines the need for prenatal initiation of therapy and also demonstrates that vacuolization alone is not the cause of clinical signs in this lysosomal storage disease in that clinical signs do not commence until at least 5 months after vacuolization is histologically apparent.

Brain Proton Magnetic Resonance Spectroscopy and Neuromuscular Pathology in a Patient With GM1 Gangliosidosis

“…However, neuropathological studies in both animal models and humans with GM 1 gangliosidosis suggest that white matter involvement (specifically oligodendrocytic dysfunction) is primarily responsible for the myelin deficits through an abnormal interaction between oligodendrocytes and neurons. [29][30][31][32] Therefore, neuronal and axonal loss, oligodendrocytic dysfunction, and dysregulation of neuronal-oligodendroglial interactions have been proposed to explain the pathophysiology of the white matter involvement occurring in infantile GM 1 gangliosidosis, as well as other lysosomal storage disorders. 33 Interestingly, the metabolic alterations detected by proton magnetic resonance spectroscopy (ie, reduction of N-acetylaspartate and increased myoinositol, suggestive of oligodendrocyte loss) are in agreement with the neuropathologic changes in our patient as well as in other previously reported cases.…”