Hereditary neurovisceral mannosidosis associated with?-mannosidase deficiency in a family of Persian cats

Abstract

Several kittens in a family of Persian cats had a metabolic storage disease. Clinically the disorder was characterized by hepatomegaly, neurological signs and early death. The microscopic lesions consisted of widespread vacuolation of neurons and glial cells in the central nervous system and in liver cells. Electronmicroscopically the lesions consisted of intracytoplasmic accumulation of membrane-bound "empty" vacuoles. In addition to the storage disease, poor myelination of the cerebral white matter was found. The defect was reproduced in breeding trials. On biochemical analysis of brain tissue, deficient function of the enzyme alpha-mannosidase was detected. The clinical and pathological features of mannosidosis in Persian cats were compared to similar defects in other species.

Apparent Diffusion Coefficient Reveals Gray and White Matter Disease, and T2 Mapping Detects White Matter Disease in the Brain in Feline Alpha-Mannosidosis

“…31 CNS pathology in feline AMD includes cellular swelling, decreased myelin, and astrogliosis. [5][6][7]12 It has been reported that AMD cats imaged at 1.5T have significant decreases in the magnetization transfer ratio (MTR) of white matter compared with normal cats, 12 whereas the MTRs were increased in cats treated with gene therapy, 14 providing evidence that MTR could be used to monitor improvements in myelination associated with therapy. These studies showed that MTR was a useful noninvasive antemortem method to quantify myelin deficiency subsequently confirmed postmortem.…”

“…2 Naturally occurring AMD has also been described in cattle, cats, and guinea pigs, and a knockout mouse has been created. [3][4][5][6][7][8][9][10] AMD cats have essentially the same clinical, biochemical, and neuropathologic abnormalities as human patients 11 and have a severe clinical phenotype with grossly obvious neurologic signs, a generally uniform disease course, and death by 6 months without treatment. 12 The feline model has proved to be useful in the evaluation of experimental therapies including bone marrow transplantation and gene therapy.…”

“…A diffuse astrogliosis of both gray and white matter is also described. 1,[5][6][7]12,15,16 MR imaging methods have been used to identify surrogate markers of gray and white matter disease in feline AMD. The magnetization transfer ratio (MTR) is sensitive for detecting white matter abnormalities in multiple sclerosis and leukodystrophies.…”

Recent progress in lysosomal α-mannosidase and its deficiency

“…Feline α-mannosidosis shows similar clinical finding, including multiple skeletal deformities, retarded growth, ataxia, intention tremors and deficiency in the acidic MANB activity (Burditt et al, 1980;Walkley et al, 1981;Vandevelde et al, 1982). In addition, the affected cats share similar phenotypic heterogeneity with the human patients, suggesting that the cats are suitable model system for studying the human disease (Raghavan et al, 1988).…”

A review of gene therapy in canine and feline models of lysosomal storage disorders

“…23,24,27 Neuropathological findings include vacuolated neurons, glia, and endothelial cells throughout the brain and spinal cord; Purkinje cell loss; and myelin deficiency of the central and peripheral nervous systems. 27 Feline alpha-mannosidosis Spontaneously occurring AMD has been reported in cats, [28][29][30][31][32][33][34] cattle, [35][36][37][38][39][40][41][42] and guinea pigs, [43][44][45] and a knockout mouse has been created. 46 Interestingly, disease can also be induced by ingestion of the indolizidine alkaloid swainsonine, which is found in locoweed plants.…”