Primary Hyperoxaluria Type II

 

Gene: GRHPR

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, GRHPR gene; g.60968927 G>A, splice site for intron 4 introducing splicing error, p.(N169K change in reading frame, STOP+46), cat chromosome D4.

Breeds: Burmese, Himalayan, Persian

Medical systems: metabolic, neurological, renal

Age of onset of symptoms: 3 to 5 months.

Primary hyperoxaluria type II is a genetic disease of the cat cause by a deficiency in the glycoxylate reductase/hydroxypyruvate reductase enzyme, coded for by the GRHPR gene.  Normally this enzyme converts the metabolic byproduct glyoxylate into the less reactive and more soluble product glycolate which is then eliminated in the urine.  Inhibited enzyme activity results in increased levels of oxalate in the blood, which will precipitate as calcium oxalate crystals within renal tubules.  This can result in acute onset kidney failure, with anorexia, dehydration and weakness in a young animal usually culminating in death.  Motor neuron denervation can additionally result in muscle atrophy and neurological signs.  A DNA test for the mutation is available.  Clinical signs of Primary Hyperoxaluria Type II in the cat can resemble ethylene glycol toxicity.

 

References:

OMIA link: [0821-9685]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

O’Kell AL, Grant DC, Khan SR. (2017) Pathogenesis of calcium oxalate urinary stone disease: species comparison of humans, dogs, and cats. Urolithiasis 45:329-336. [pubmed/28361470]

Goldstein RE, Narala S, Sabet N, et al. (2009) Primary hyperoxaluria in cats is caused by a mutation in the feline GRHPR gene. J Hered 100 (Suppl. 1):S2-S7, 2009. https://academic.oup.com/jhered/article/100/suppl_1/S2/896719

Osborne CA, Lulich JP, Kruger JM, et.al. (2009) 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. [pubmed/19038658]

 

Contributed by: Anabelle Perron and Charlie Dufour, Class of 2027, Faculté de médecine vétérinaire, Université de Montréal.   (Translation DWS).