OMIA:000664-9685 : Mucopolysaccharidosis I in Felis catus (domestic cat)

In other species: dog , taurine cattle

Categories: Lysosomal storage disease

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 607014 (trait) , 607015 (trait) , 607016 (trait) , 252800 (gene)

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: 1999

Cross-species summary: Also known as Hurler syndrome

Species-specific description: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease characterized by intracellular accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfates. Affected cats have flat, broad faces, large heads, small ears, thick skin over the dorsal neck, wide cervical vertebrae, and hip subluxation. Other signs include abnormal gait, corneal clouding and some have a cardiac murmur of mitral insufficiency. The mode of inheritance is autosomal recessive, and the causative mutation is a 3 base-pair deletion in the IUDA gene. Affected cats are deficient in the lysosomal enzyme alpha-L-iduronidase, which is a part of the breakdown pathway of glycosaminoglycans. Since affected cats cannot adequately break down the GAGs, they accumulate in multiple cell types and cause clinical signs. There is a test available to detect the mutation. Siblings of affected cats should be tested. Breeding of affected or carrier cats should be avoided. Edited by Mark Haskins, VMD, PhD

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), He et al. (1999) showed that the causative mutation is a 3 bp deletion in the IDUA gene, which results in removal of an aspartate residue from the finished polypeptide.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Affected cats have flat, broad faces, large heads, small ears, thick skin over the dorsal neck, wide cervical vertebrae, and hip subluxation. Other signs include abnormal gait, corneal clouding and some have a cardiac murmur of mitral insufficiency. Fine metachromatic granules occur in lymphocytes. GAGs are detectable in urine by a simple alcian-blue spot test (Haskins et al., 1979, Haskins et al., 1983).

Pathology: Affected cats are deficient in the lysosomal enzyme alpha-L-iduronidase, which is a part of the breakdown pathway of glycosaminoglycans. It is a hydrolase that removes iduronic acid residues from dermatan sulfate and heparan sulfate. Since affected cats cannot adequately break down the GAGs, they accumulate in multiple cell types and cause clinical signs (He et al., 1999). Thickened cardiac valves and cordae tendinae, and cerebral ventricle dilatation are observable on necropsy, along with a wide cervical spine (Haskins et al., 1979). Membrane-bound cytoplasmic inclusions aggregate in hepatocytes, Kupffer cells, fibroblasts, cartilage, cornea, retinal pigment epithelial cells, neurons, and white blood cells. These cells can appear to have vacuolated cytoplasm on histologic examination (Haskins et al., 1979). On examination by electron microscopy, brain and spinal cord neurons contain membrane-bound “zebra bodies” (He et al., 1999).

Prevalence: Southeastern Pennsylvania

Control: Siblings of affected cats should be tested. Breeding of affected or carrier cats should be avoided.

Genetic testing: There is a test available to detect the mutation.

Breed: Domestic Shorthair.
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
IDUA iduronidase, alpha-L- Felis catus B1 NC_058371.1 (204948412..204933314) IDUA 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.

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
500 Mucopolysaccharidosis I IDUA deletion, small (<=20) Naturally occurring variant Felis_catus_9.0 B1 g.207800586_207800588del c.1042_1044del p.(D348del) NM_001305032.1; NP_001291961.1; a 3 bp deletion in the IDUA gene; HGVS 3'-rule applied to variant coordinates in this table 1999 10356309 Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley.

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2012). OMIA:000664-9685: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2020 Hampe, C.S., Polgreen, L.E., Lund, T.C., McIvor, R.S. :
Dysostosis multiplex in human mucopolysaccharidosis type 1 H and in animal models of the disease. Pediatr Endocrinol Rev 17:317-326, 2020. Pubmed reference: 32780955. DOI: 10.17458/per.vol17.2020.hpl.dysostosismultiplexhumananimal.
2014 Hinderer, C., Bell, P., Gurda, B.L., Wang, Q., Louboutin, J.P., Zhu, Y., Bagel, J., O'Donnell, P., Sikora, T., Ruane, T., Wang, P., Haskins, M.E., Wilson, J.M. :
Intrathecal gene therapy corrects CNS pathology in a feline model of mucopolysaccharidosis I. Mol Ther 22:2018-27, 2014. Pubmed reference: 25027660. DOI: 10.1038/mt.2014.135.
Hinderer, C., Bell, P., Gurda, B.L., Wang, Q., Louboutin, J.P., Zhu, Y., Bagel, J., O'Donnell, P., Sikora, T., Ruane, T., Wang, P., Haskins, M.E., Wilson, J.M. :
Liver-directed gene therapy corrects cardiovascular lesions in feline mucopolysaccharidosis type I. Proc Natl Acad Sci U S A 111:14894-9, 2014. Pubmed reference: 25267637. DOI: 10.1073/pnas.1413645111.
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.
2011 Cianciolo, R.E., Rhodes, J.L., Haskins, M.E., Clubb, F.J., Lees, G.E. :
Renal failure associated with mucopolysaccharidosis type I in a cat from a MPS I research colony. Comp Med 61:441-4, 2011. Pubmed reference: 22330352.
Vite, C.H., Wang, P., Patel, R.T., Walton, R.M., Walkley, S.U., Sellers, R.S., Ellinwood, N.M., Cheng, A.S., White, J.T., O'Neill, C.A., Haskins, M. :
Biodistribution and pharmacodynamics of recombinant human alpha-L-iduronidase (rhIDU) in mucopolysaccharidosis type I-affected cats following multiple intrathecal administrations. Mol Genet Metab 103:268-74, 2011. Pubmed reference: 21482164. DOI: 10.1016/j.ymgme.2011.03.011.
2008 Lischka, FW., Gomez, G., Yee, KK., Dankulich-Nagrudny, L., Lo, L., Haskins, ME., Rawson, NE. :
Altered olfactory epithelial structure and function in feline models of mucopolysaccharidoses I and VI. J Comp Neurol 511:360-72, 2008. Pubmed reference: 18803239. DOI: 10.1002/cne.21847.
Sleeper, MM., Kusiak, CM., Shofer, FS., O'Donnell, P., Bryan, C., Ponder, KP., Haskins, ME. :
Clinical characterization of cardiovascular abnormalities associated with feline mucopolysaccharidosis I and VI. J Inherit Metab Dis 31:424-31, 2008. Pubmed reference: 18509743. DOI: 10.1007/s10545-008-0821-1.
2007 Ellinwood, NM., Colle, MA., Weil, MA., Casal, ML., Vite, CH., Wiemelt, S., Hasson, CW., O'Malley, TM., He, X., Prociuk, U., Verot, L., Melniczek, JR., Lannon, A., Aguirre, GD., Knox, VW., Evans, SM., Vanier, MT., Schuchman, EH., Walkley, SU., Haskins, ME. :
Bone marrow transplantation for feline mucopolysaccharidosis I. Mol Genet Metab 91:239-50, 2007. Pubmed reference: 3145485.
2001 Kakkis, E.D., Schuchman, E., He, X., Wan, Q., Kania, S., Wiemelt, S., Hasson, C.W., O'Malley, T., Weil, M.A., Aguirre, G.A., Brown, D.E., Haskins, M.E. :
Enzyme replacement therapy in feline mucopolysaccharidosis I Molecular Genetics &amp; Metabolism 72:199-208, 2001. Pubmed reference: 11243725. DOI: 10.1006/mgme.2000.3140.
1999 He, X.X., Li, C.M., Simonaro, C.M., Wan, Q., Haskins, M.E., Desnick, R.J., Schuchman, E.H. :
Identification and characterization of the molecular lesion causing mucopolysaccharidosis type I in cats Molecular Genetics and Metabolism 67:106-112, 1999. Pubmed reference: 10356309. DOI: 10.1006/mgme.1999.2860.
1996 Mollard, R.J., Telegan, P., Haskins, M., Aguirre, G. :
Corneal endothelium in mucopolysaccharide storage disorders. Morphologic studies in animal models. Cornea 15:25-34, 1996. Pubmed reference: 8907377.
1994 Sheridan, O., Wortman, J., Harvey, C., Hayden, J., Haskins, M. :
Craniofacial abnormalities in animal models of mucopolysaccharidoses I, VI, and VII. J Craniofac Genet Dev Biol 14:7-15, 1994. Pubmed reference: 8006122.
1992 Haskins, M.E., Otis, E.J., Hayden, J.E., Jezyk, P.F., Stramm, L. :
Hepatic Storage of Glycosaminoglycans in Feline and Canine Models of Mucopolysaccharidose-I, Mucopolysaccharidose-VI, and Mucopolysaccharidose-VII Veterinary Pathology 29:112-119, 1992. Pubmed reference: 1632054.
1987 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.
1983 Haskins, M.E., Aguirre, G.D., Jezyk, P.F., Desnick, R.J., Patterson, D.F. :
The pathology of the feline model of mucopolysaccharidosis I. Am J Pathol 112:27-36, 1983. Pubmed reference: 6407329.
1979 Haskins, M.E., Jezyk, P.F., Desnick, R.J., McDonough, S.K., Patterson, D.F. :
Alpha-L- iduronidase deficiency in a cat: a model of mucopolysaccharidosis I Pediatric Research 13:1294-1297, 1979. Pubmed reference: 117422.

Edit History


  • Created by Frank Nicholas on 26 Nov 2007
  • Changed by Martha MaloneyHuss on 17 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 07 Oct 2011
  • Changed by Frank Nicholas on 17 Nov 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 03 Feb 2012
  • Changed by Frank Nicholas on 20 Feb 2012
  • Changed by Matthew Hobbs on 20 Mar 2012
  • Changed by Frank Nicholas on 15 Sep 2012