OMIA 000821-9685 : Hyperoxaluria, primary, type II (Oxalosis II) in Felis catus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 260000 (trait) , 604296 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2009

Species-specific symbol: PH2

Species-specific description: Acute-onset renal failure in young cats (<1 year of age) from deposition of oxalate crystals in renal tubules. Type II oxalosis is characterized by an increase in L-glyceric acid in the urine compared to type I oxalosis where glycolate and glyoxylate are increasingly excreted in the urine (McKerrell et al., 1989). Hyperoxaluria induces acute renal failure with recurrent calcium oxalate nephrolithiasis (Osborne et al., 2009).

Cats have experienced a 10-fold increase in frequency of nephroliths in the past 20 years- of which calcium oxalate make up 70% of those uroliths (Osborne et al., 2009). Risk factors for calcium oxalate nephroliths include breed, neutered male status, 10 years of age, aciduria, hypercalciuria, hypercalcemia, hyperoxaluria, indoor status (reduced water intake, reduced urine output, obesity), and diets that are acidifying and restricting magnesium (Osborne et al., 2009; Lekcharoensuk et al. 2000). 56% of cats with uroliths suffer from chronic kidney disease (Osborne et al., 2009).

(Compiled by Rachel Natsume 13/9/2021)

Molecular basis: By sequencing the most likely comparative candidate gene (based on clinical signs), Goldstein et al. (2009) identified a causal mutation as a "point mutation, G to A, . . . at the 3# splice acceptor site of intron 4". They speculated "that the lack of the necessary terminal AG sequence of intron 4 would result in a misplicing event. This would result in the splicing out of exon 5, resulting in a shortened and abnormal mRNA and protein."

Clinical features: Development of azotemia and neurological signs develop between 5 and 9 months of age (McKerrell et al., 1989). “The onset of signs was generally acute, with the development of anorexia, dehydration and weakness occurring over a few days … . Acutely ill cats were depressed, dehydrated and in poor bodily condition. Palpation of the abdomen revealed painful kidneys which were irregular in outline and frequently thought to be enlarged. In two cases the kidneys were shrunken. Deterioration was rapid...” (McKerrell et al., 1989). Generalized muscle atrophy occurs as a result of denervation of motor neurons and accumulation of neurofilaments in the spinal motor neurons (De Lorenzi et al., 2005). Spinal reflexes may be reduced to absent (De Lorenzi et al., 2005). Ethylene glycol toxicity (antifreeze) produces a similar clinical presentation of acute renal failure with histological evidence of renal oxalosis (McKerrell et al., 1989). Ultrasound examination of the kidneys can differentiate the cause of renal oxalosis by the echogenicity of the renal parenchyma.

(Compiled by Rachel Natsume 13/9/2021)

Pathology: An excess of circulating oxalate accumulates in the renal tubules as calcium oxalate crystals. “Blood analysis and urinalysis showed several abnormalities, including intermittent hyperoxaluria. The L-glyceric acid concentration was remarkably increased. Electrodiagnostic tests of the peripheral nervous system were abnormal. At necropsy, generalized muscle atrophy was observed. Microscopically, both kidneys showed intraluminal birefringent oxalate crystals. Motor neuron degeneration and accumulation of neurofilaments were observed in the axons of the spinal motor neurons.” (De Lorenzi et al., 2005). There is a deficiency in DGDH liver enzyme analogous to the human form of primary hyperoxaluria type II (McKerrell et al., 1989).

(Compiled by Rachel Natsume 13/9/2021)

Breeds: Burmese, Himalayan, Persian.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GRHPR glyoxylate reductase/hydroxypyruvate reductase Felis catus D4 NC_058380.1 (58926318..58938173) GRHPR Homologene, Ensembl, NCBI gene

Variants

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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
383 Primary hyperoxaluria type II (Oxalosis II) GRHPR splicing Naturally occurring variant Felis_catus_9.0 D4 g.60968927G>A p.(N169Kfs*46) "point mutation, G to A, . . . at the 3# splice acceptor site of intron 4" ; protein position based on XP_006939354.1 2009 Reference not in PubMed; see OMIA 000821-9685 for reference details

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.
2017 O'Kell, A.L., Grant, D.C., Khan, S.R. :
Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats. Urolithiasis 45:329-336, 2017. Pubmed reference: 28361470. DOI: 10.1007/s00240-017-0978-x.
2012 Suzuki, T., Uetsuka, K., Doi, K., Nunoya, T. :
A case of renal oxalosis in a 3-month-old cat raised under controlled conditions. J Vet Med Sci 74:381-4, 2012. Pubmed reference: 22067080. DOI: 10.1292/jvms.11-0399.
2009 Gisselman, K., Langston, C., Palma, D., McCue, J. :
Calcium oxalate urolithiasis. Compend Contin Educ Vet 31:496-502; quiz 502, 2009. Pubmed reference: 20180219.
Goldstein, RE., Narala, S., Sabet, N., Goldstein, O., McDonough, SP. :
Primary hyperoxaluria in cats is caused by a mutation in the feline GRHPR gene. J Hered 100 (Suppl. 1):S2-S7, 2009. DOI: https://doi.org/10.1093/jhered/esp038.
Heiene, R., Rumsby, G., Ziener, M., Dahl, S.A., Tims, C., Teige, J., Ottesen, N. :
Chronic kidney disease with three cases of oxalate-like nephrosis in Ragdoll cats. J Feline Med Surg 11:474-80, 2009. Pubmed reference: 19095478. DOI: 10.1016/j.jfms.2008.11.003.
Osborne, C.A., Lulich, J.P., Kruger, J.M., Ulrich, L.K., Koehler, L.A. :
Analysis of 451,891 canine uroliths, feline uroliths, and feline urethral plugs from 1981 to 2007: perspectives from the Minnesota Urolith Center. Vet Clin North Am Small Anim Pract 39:183-97, 2009. Pubmed reference: 19038658. DOI: 10.1016/j.cvsm.2008.09.011.
2006 Sewell, A.C. :
Feline primary hyperoxaluria. J Feline Med Surg 8:290, 2006. Pubmed reference: 16603399. DOI: 10.1016/j.jfms.2006.02.001.
2005 De Lorenzi, D., Bernardini, M., Pumarola, M. :
Primary hyperoxaluria (L-glyceric aciduria) in a cat. J Feline Med Surg 7:357-61, 2005. Pubmed reference: 15914058. DOI: 10.1016/j.jfms.2005.03.007.
Lekcharoensuk, C., Osborne, C.A., Lulich, J.P., Albasan, H., Ulrich, L.K., Koehler, L.A., Carpenter, K.A., Swanson, L.L., Pederson, L.A. :
Trends in the frequency of calcium oxalate uroliths in the upper urinary tract of cats. J Am Anim Hosp Assoc 41:39-46, 2005. Pubmed reference: 15634865. DOI: 10.5326/0410039.
2001 Greco, D.S. :
Congenital and inherited renal disease of small animals. Vet Clin North Am Small Anim Pract 31:393-9, viii, 2001. Pubmed reference: 11265498. DOI: 10.1016/s0195-5616(01)50211-9.
2000 Lekcharoensuk, C., Lulich, J.P., Osborne, C.A., Koehler, L.A., Urlich, L.K., Carpenter, K.A., Swanson, L.L. :
Association between patient-related factors and risk of calcium oxalate and magnesium ammonium phosphate urolithiasis in cats Journal of the American Veterinary Medical Association 217:520-525, 2000. Pubmed reference: 10953716.
1989 Danpure, C.J., Jennings, P.R., Mistry, J., Chalmers, R.A., Mckerrell, R.E., Blakemore, W.F., Heath, M.F. :
Enzymological characterization of a feline analogue of primary hyperoxaluria type-2 - A model for the human disease. Journal of Inherited Metabolic Disease 12:403-414, 1989. Pubmed reference: 2516173.
McKerrell, RE., Blakemore, WF., Heath, MF., Plumb, J., Bennett, MJ., Pollitt, RJ., Danpure, CJ. :
Primary hyperoxaluria (L-glyceric aciduria) in the cat: a newly recognised inherited disease. Vet Rec 125:31-4, 1989. Pubmed reference: 2773220.
1988 Blakemore, WF., Heath, MF., Bennett, MJ., Cromby, CH., Pollitt, RJ. :
Primary hyperoxaluria and L-glyceric aciduria in the cat. J Inherit Metab Dis 11 Suppl 2:215-7, 1988. Pubmed reference: 3141705.

Edit History


  • Created by Frank Nicholas on 01 Jul 2009
  • Changed by Frank Nicholas on 07 Oct 2011
  • Changed by Frank Nicholas on 04 Dec 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 18 Jun 2013
  • Changed by Imke Tammen2 on 13 Sep 2021