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

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Abstract
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 GM1 gangliosidosis, but is unique in that a genetic defect in lysosomal β‐galactosidase may cause the deficiency of lysosomal α‐neuraminidase.