Hexa-associated GM2 gangliosidosis in a family of wild boars

Gangliosidosis are inherited lysosomal storage disorders caused by defective activity of a lysosomal hydrolase required for ganglioside catabolism, resulting in the intra-lysosomal accumulation of undegraded metabolites. The molecular mechanisms linking the lysosomal accumulation to the pathology are still obscure. We report on a novel form of GM2 gangliosidosis in wild boar (Sua scrofa). Three littermate wild boards, from a free ranging farm, presented neurological signs (dysmetria, ataxia, quadriplegia and lateral decubitus) at 6 months of age. Viral, bacterial and toxicological analysis were performed to esclude possible exogenous causes of symptoms. Animale were euthanazed at approximately one year of age. Necropsy revealed in all affected animali reduced consistency of cerebral and cerebellar parenchyma. Histology revealed enlarged foamy neuroni, with diffusely severely vacuolated cytoplasm in brain, cerebellum, spinal cord, peripheral ganglia and retina. EM revealed the presente in neurons of numerous lysosomes, filled by membranous material. Biochemical studies revealed the presente of an elevate amount of GM2 ganglioside, confirming the diagnosis of GM2 gangliosidosis. In addition, genetic analysis revealed the presence of a recessively inherited missense variano (p.Arg499Cys) in the hexo.saminidase subiinit alpha (UW2 gene located within the GH20 hexosaminidase superfamily domain of the encoded protein. In man and other species, pathogenic HEXA variante are known to be associated with the disease. In conclusion, this HEXA-associated form ot GM2 gangliosidosis, described for the first time in wild boars, is thus very similar to human disease.