OMIA 000664-9685 : Mucopolysaccharidosis I in Felis catus

In other species: dog , cattle

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

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.

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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
IDUA iduronidase, alpha-L- Felis catus B1 NC_018726.3 (207813501..207798427) IDUA Homologene, Ensembl, NCBI gene

Variants

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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
Mucopolysaccharidosis I IDUA deletion, small (<=20) a 3 bp deletion in the IDUA gene 1999 10356309

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.
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.
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.
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
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  • Changed by Frank Nicholas on 07 Oct 2011
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