Inherited lysosomal storage disease associated with deficiencies of β-galactosidase and α-neuraminidase in sheep

Histopathologic, ultrastructural and Golgi impregnation studies disclosed lesions characteristic of a neuronal lysosomal storage disease in related sheep with onset of neurologic signs at 4-6 months. Biochemical and enzymatic evaluation disclosed storage of GM₁ ganglioside, asialo-GM₁, and neutral long chain oligosaccharides in brain, urinary excretion of neutral long chain oligosaccharides, and deficiencies of lysosomal β-galactosidase and α-neuraminidase. Retrospective and limited prospective genetic studies suggested autosomal recessive inheritance. A gene-dosage effect on β-galactosidase levels was documented in fibroblasts from putative heterozygous sheep. Fibroblasts from affected sheep did not have increased β-galactosidase activity after incubation with the protease inhibitor, leupeptin. In some aspects this disease is similar to GM₁ gangliosidosis, but is unique in that a genetic defect in lysosomal β-galactosidase may cause the deficiency of lysosomal α-neuraminidase.