title: Inherited lysosomal storage disease associated with deficiencies of beta-galactosidase and alpha-neuraminidase in sheep.
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 beta-galactosidase and alpha-neuraminidase. Retrospective and limited prospective genetic studies suggested autosomal recessive inheritance. A gene-dosage effect on beta-galactosidase levels was documented in fibroblasts from putative heterozygous sheep. Fibroblasts from affected sheep did not have increased beta-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 beta-galactosidase may cause the deficiency of lysosomal alpha-neuraminidase.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ahern-Rindell
authors.forename: D J
authors.initials: DJ
authors.lastname: Prieur
authors.forename: R D
authors.initials: RD
authors.lastname: Murnane
authors.forename: S S
authors.initials: SS
authors.lastname: Raghavan
authors.forename: P F
authors.initials: PF
authors.lastname: Daniel
authors.forename: R H
authors.initials: RH
authors.lastname: McCluer
authors.forename: S U
authors.initials: SU
authors.lastname: Walkley
authors.forename: S M
authors.initials: SM
authors.lastname: Parish
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D002460:Cell Line; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005696:Galactosidases / Q000172:deficiency*; D008055:Lipids / Q000302:isolation & purification; D008297:Male; D008854:Microscopy, Electron; D009439:Neuraminidase / Q000172:deficiency*; D009474:Neurons / Q000166:cytology / Q000648:ultrastructure; D009844:Oligosaccharides / Q000032:analysis / Q000652:urine; D010375:Pedigree; D012756:Sheep; D012757:Sheep Diseases / Q000201:enzymology / Q000235:genetics*; D012867:Skin / Q000201:enzymology; D013116:Spinal Cord / Q000473:pathology; D001616:beta-Galactosidase / Q000172:deficiency*
chemical_list: D008055:Lipids; D009844:Oligosaccharides; D005696:Galactosidases; D009439:Neuraminidase; D001616:beta-Galactosidase