OMIA 000625-9685 : Mannosidosis, alpha in Felis catus
Category: Lysosomal storage disease
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 1997
Cross-species summary: A lysosomal storage disease in which there is a buildup (storage) of mannose-rich compounds, due to the lack of the enzyme alpha-mannosidase, whose task is to cleave mannose from such compounds. Clinical signs include ataxia, head tremor, aggression, and finally paralysis and death.
Species-specific description: Alpha-mannosidosis is a lysosomal storage disease characterized by accumulation of mannose-rich oligosaccharides in lysosomes. Clinical signs include neurological deficits, skeletal deformities, growth retardation, gingival hyperplasia, and corneal and lenticular opacities. Affected cats are deficient in the lysosomal hydrolase alpha-mannosidase, which is necessary for the degradation of glycoproteins. In the absence of sufficient alpha-mannosidase, mannose-rich oligosaccharides accumulate intracellularly. Upon histopathologic examination, vacuolated neurons, glial cells, and endothelial cells are present throughout the central nervous system. The mode of inheritance is autosomal recessive. The causative mutation is a 4 base pair deletion in the gene coding for lysosomal alpha-mannosidase. There is a test available to detect the mutation. Siblings of affected cats should be tested. Breeding of affected or carrier cats is not recommended.
Edited by Mark Haskins, VMD, PhD
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Berg et al. (1997) identified a causative variant as a 4-base-pair deletion in the gene coding for lysosomal alpha-mannosidase, resulting in "a frame shift from codon 583 and premature termination at codon 645". This variant is specific to Persian cats and was not found in Domestic Longhair cat with alpha-mannosidosis. According to the variant nomencalture of the years 2013 this variant corresponds to c.1749_1752delCCAG or p.Q584Afs.
Clinical features: Cats with alpha-mannosidosis have severe neurological deficits, tremors, loss of balance, nystagmus, hearing loss, synovitis, dorsoventral narrowing of the palpebral fissure, hydrocephalus, skeletal deformities, growth retardation, gingival hyperplasia, and corneal and lenticular opacities. Without treatment, life expectancy is about six months (Abkowitz et al., 2009, Vite et al., 2001). Urinary oligosaccarides can be detected by thin-layer chromatography.
Pathology: Affected cats are deficient in the lysosomal hydrolase alpha-mannosidase, which is necessary for the degradation of glycoproteins. In the absence of sufficient alpha-mannosidase, mannose-rich oligosaccharides accumulate intracellularly. Upon histopathologic examination, vacuolated neurons, glial cells, and endothelial cells are present throughout the central nervous system. The centrum semiovale and the cerebellar white matter appear to be deficient in myelin. There are fewer Purkinje cells and granular neurons than normal in the cerebellum (Vite et al., 2001).
Control: Siblings of affected cats should be tested. Breeding of affected or carrier cats is not recommended.
Genetic testing: There is a test available to detect the mutation.
Breeds: Domestic Longhair, Domestic Shorthair, Persian (Cat) (VBO_0100188).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MAN2B1||mannosidase, alpha, class 2B, member 1||Felis catus||A2||NC_058369.1 (8965933..8950052)||MAN2B1||Homologene, Ensembl, NCBI gene|
By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.
WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|499||Mannosidosis, alpha||MAN2B1||deletion, small (<=20)||Naturally occurring variant||Felis_catus_9.0||A2||g.9011118_9011121del||c.1749_1752del||p.(Q584Afs)||NM_001009222.1; NP_001009222.1||1997||9396732||Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley.|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2016||Yoon, S.Y., Bagel, J.H., O'Donnell, P.A., Vite, C.H., Wolfe, J.H. :>|
|Clinical improvement of alpha-mannosidosis cat following a single cisterna magna infusion of AAV1. Mol Ther 24:26-33, 2016. Pubmed reference: 26354342. DOI: 10.1038/mt.2015.168.|
|2015||Kumar, M., Duda, J.T., Yoon, S.Y., Bagel, J., O'Donnell, P., Vite, C., Pickup, S., Gee, J.C., Wolfe, J.H., Poptani, H. :>|
|Diffusion tensor imaging for assessing brain gray and white matter abnormalities in a feline model of α-mannosidosis. J Neuropathol Exp Neurol :, 2015. Pubmed reference: 26671987. DOI: 10.1093/jnen/nlv007.|
|2012||Sewell, A.C., Haskins, M.E., Giger, U. :>|
|Dried blood spots for the enzymatic diagnosis of lysosomal storage diseases in dogs and cats. Vet Clin Pathol 41:548-57, 2012. Pubmed reference: 23121383. DOI: 10.1111/j.1939-165x.2012.00485.x.|
|2010||Magnitsky, S., Vite, C.H., Delikatny, E.J., Pickup, S., Wehrli, S., Wolfe, J.H., Poptani, H. :>|
|Magnetic resonance spectroscopy of the occipital cortex and the cerebellar vermis distinguishes individual cats affected with alpha-mannosidosis from normal cats. NMR Biomed 23:74-9, 2010. Pubmed reference: 19743435. DOI: 10.1002/nbm.1430.|
|2009||Abkowitz, JL., Sabo, KM., Yang, Z., Vite, CH., Shields, LE., Haskins, ME. :>|
|In utero transplantation of monocytic cells in cats with alpha-mannosidosis. Transplantation 88:323-9, 2009. Pubmed reference: 19667933. DOI: 10.1097/TP.0b013e3181b0d264.|
|Khan, J.M., Ranganathan, S. :>|
|A multi-species comparative structural bioinformatics analysis of inherited mutations in alpha-D-mannosidase reveals strong genotype-phenotype correlation. BMC Genomics :S33, 2009. Pubmed reference: 19958498. DOI: 10.1186/1471-2164-10-S3-S33.|
|2008||Vite, C.H., Magnitsky, S., Aleman, D., O'Donnell, P., Cullen, K., Ding, W., Pickup, S., Wolfe, J.H., Poptani, H. :>|
|Apparent diffusion coefficient reveals gray and white matter disease, and T2 mapping detects white matter disease in the brain in feline alpha-mannosidosis. AJNR Am J Neuroradiol 29:308-13, 2008. Pubmed reference: 17974615. DOI: 10.3174/ajnr.A0791.|
|2001||Vite, C.H., McGowan, J.C., Braund, K.G., Drobatz, K.J., Glickson, J.D., Wolfe, J.H., Haskins, M.E. :>|
|Histopathology, electrodiagnostic testing, and magnetic resonance imaging show significant peripheral and central nervous system myelin abnormalities in the cat model of alpha-mannosidosis. J Neuropathol Exp Neurol 60:817-28, 2001. Pubmed reference: 11487056.|
|1999||Sun, H., Yang, M., Haskins, M.E., Patterson, D.F., Wolfe, J.H. :>|
|Retrovirus vector-mediated correction and cross-correction of lysosomal alpha-mannosidase deficiency in human and feline fibroblasts Human Gene Therapy 10:1311-1319, 1999. Pubmed reference: 10365662. DOI: 10.1089/10430349950017996.|
|1997||Berg, T., Tollersrud, O.K., Walkley, S.U., Siegel, D., Nilssen, O. :>|
|Purification of feline lysosomal alpha-mannosidase, determination of its cdna sequence and identification of a mutation causing alpha-mannosidosis in Persian cats Biochemical Journal 328:863-870, 1997. Pubmed reference: 9396732.|
|1992||Degasperi, R., Aldaher, S., Winchester, B.G., Warren, C.D. :>|
|Substrate specificity of the bovine and feline neutral alpha-mannosidases Biochemical Journal 286:55-63, 1992. Pubmed reference: 1520284.|
|1991||Alroy, J., Bachrach, A., Thalhammer, J.G., Panjwani, N., Richard, R., DeGasperi, R., Warren, C.D., Albert, D.M., Raghavan, S.S. :>|
|Clinical, neurophysiological, biochemical and morphological features of eyes in Persian cats with mannosidosis. Virchows Arch B Cell Pathol Incl Mol Pathol 60:173-80, 1991. Pubmed reference: 1679268. DOI: 10.1007/BF02899544.|
|Degasperi, R., Aldaher, S., Daniel, P.F., Winchester, B.G., Jeanloz, R.W., Warren, C.D. :>|
|The substrate specificity of bovine and feline lysosomal alpha-D-mannosidases in relation to alpha-mannosidosis Journal of Biological Chemistry 266:16556-16563, 1991. Pubmed reference: 1885586.|
|Hard, K., Mekking, A., Kamerling, J.P., Dacremont, G.A.A., Vliegenthart, J.F.G. :>|
|Different oligosaccharides accumulate in the brain and urine of a cat with alpha-mannosidosis - Structure determination of five brain-derived and seventeen urinary oligosaccharides Glycoconjugate Journal 8:17-28, 1991. Pubmed reference: 1668528.|
|1990||Castagnaro, M. :>|
|Lectin histochemistry of the central nervous system in a case of feline alpha-mannosidosis. Res Vet Sci 49:375-7, 1990. Pubmed reference: 2267428.|
|1989||Alroy, J., Freden, G.O., Goyal, V., Raghavan, S.S., Schunk, K.L. :>|
|Morphology of leukocytes from cats affected with alpha-mannosidosis and mucopolysaccharidosis-VI (MPS-VI) Veterinary Pathology 26:294-302, 1989. Pubmed reference: 2503918.|
|1988||[No authors listed] :>|
|The accumulation of oligosaccharides in tissues and body fluids of cats with alpha-mannosidosis. Carbohydr Res 180:325-38, 1988. Pubmed reference: 3203344. DOI: 10.1016/0008-6215(88)80089-2.|
|Cummings, J.F., Wood, P.A., de Lahunta, A., Walkley, S.U., Le Boeuf, L. :>|
|The clinical and pathologic heterogeneity of feline alpha-mannosidosis. J Vet Intern Med 2:163-70, 1988. Pubmed reference: 3230555.|
|Maenhout, T., Kint, J.A., Dacremont, G., Ducatelle, R., Leroy, J.G., Hoorens, J.K. :>|
|Mannosidosis in a litter of Persian cats. Vet Rec 122:351-4, 1988. Pubmed reference: 3381451. DOI: 10.1136/vr.122.15.351.|
|Raghavan, S., Stuer, G., Riviere, L., Alroy, J., Kolodny, E.H. :>|
|Characterization of alpha-mannosidase in feline mannosidosis. J Inherit Metab Dis 11:3-16, 1988. Pubmed reference: 3128686. DOI: 10.1007/BF01800052.|
|1987||Alroy, J., Warren, C.D., Raghavan, S.S., Daniel, P.F., Schunk, K.L., Kolodny, E.H. :>|
|Biochemical, ultrastructural and histochemical studies of cat placentae deficient in activity of lysosomal alpha-mannosidase. Placenta 8:545-53, 1987. Pubmed reference: 3422924. DOI: 10.1016/0143-4004(87)90083-x.|
|Castagnaro, M., Alroy, J., Ucci, A.A., Glew, R.H. :>|
|Lectin histochemistry and ultrastructure of feline kidneys from six different storage diseases. Virchows Arch B Cell Pathol Incl Mol Pathol 54:16-26, 1987. Pubmed reference: 2892300. DOI: 10.1007/BF02899193.|
|1986||Abraham, D., Daniel, P., Dell, A., Oates, J., Sidebotham, R., Winchester, B. :>|
|Structural analysis of the major urinary oligosaccharides in feline alpha-mannosidosis. Biochem J 233:899-904, 1986. Pubmed reference: 3707532. DOI: 10.1042/bj2330899.|
|Jezyk, P.F., Haskins, M.E., Newman, L.R. :>|
|Alpha-mannosidosis in a Persian cat. J Am Vet Med Assoc 189:1483-5, 1986. Pubmed reference: 3804848.|
|Warren, C.D., Alroy, J., Bugge, B., Daniel, P.F., Raghavan, S.S., Kolodny, E.H., Lamar, J.J., Jeanloz, R.W. :>|
|Oligosaccharides from placenta: early diagnosis of feline mannosidosis. FEBS Lett 195:247-52, 1986. Pubmed reference: 3943609. DOI: 10.1016/0014-5793(86)80169-7.|
|1983||Abraham, D., Blakemore, W.F., Jolly, R.D., Sidebotham, R., Winchester, B. :>|
|The catabolism of mammalian glycoproteins. Comparison of the storage products in bovine, feline and human mannosidosis. Biochem J 215:573-9, 1983. Pubmed reference: 6661184. DOI: 10.1042/bj2150573.|
|1982||Vandevelde, M., Fankhauser, R., Bichsel, P., Wiesmann, U., Herschkowitz, N. :>|
|Hereditary neurovisceral mannosidosis associated with alpha-mannosidase deficiency in a family of Persian cats. Acta Neuropathol 58:64-8, 1982. Pubmed reference: 7136518.|
|1981||Walkley, S.U., Blakemore, W.F., Purpura, D.P. :>|
|Alterations in neuron morphology in feline mannosidosis. A Golgi study. Acta Neuropathol 53:75-9, 1981. Pubmed reference: 7211201. DOI: 10.1007/BF00697187.|
|1980||Egger, G.J., Webb, R.A., Reynolds, I., Burditt, L.J., Chotai, K., Hirani, S., Nugent, P.G., Winchester, B.G., Blakemore, W.F. :>|
|Biochemical studies on a case of feline mannosidosis. Biochem J 189:467-73, 1980. Pubmed reference: 7213340. DOI: 10.1042/bj1890467.|
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