OMIA 000625-9685 : Mannosidosis, alpha in Felis catus

In other species: cattle , sheep , domestic guinea pig , goat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 248500

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*179.

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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MAN2B1 mannosidase, alpha, class 2B, member 1 Felis catus A2 NC_018724.3 (9021069..9005210) MAN2B1 Homologene, Ensembl, NCBI gene

Variants

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Mannosidosis, alpha MAN2B1 deletion, small (<=20) c.1749_1752delCCAG p.Q584Afs*179 1997 9396732

References


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 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.
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 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.
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.

Edit History


  • Created by Frank Nicholas on 10 Sep 2005
  • Changed by Martha MaloneyHuss on 17 Aug 2011
  • Changed by Martha MaloneyHuss on 23 Aug 2011
  • Changed by Vicki Meyers-Wallen on 18 Sep 2011
  • Changed by Vicki Meyers-Wallen on 27 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 03 Sep 2012
  • Changed by Tosso Leeb on 29 May 2013