PH I

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Primary hyperoxaluria type I (PH I) in Coton de Tulear


Primary hyperoxaluria (PH) is a rare autosomal recessive disorder of glyoxylate metabolism in humans that was also described in dogs (Jansen &Arnesen 1990; Danpure et al. 1991, Vidgren et al. 2012) and cats (Goldstein et al. 2009).  It is characterized by the accumulation of oxalate and subsequent precipitation of calcium oxalate crystals, primarily in the kidneys, leading to progressive kidney failure. If the storage capacity of the kidneys is exhausted, the crystals are accumulated in other tissues, for example in bones, joints, cartilages, retina and muscles.

The PH disease is caused by insufficient function of a liver-specific enzyme alanine -glyoxalate aminotransferase (AGT, AGXT) or an enzyme possessing both glyoxalate reductase and hydroxyl-pyruvate reductase activities (GRHPR). Lack of these enzymes occurs in 95% of animals affected with PH.  Lack of AGXT results in more serious form of the disease with earlier disease onset designated as PH I and the lack of GRHPR-enzyme causes the PH II-form.

In connection with PH I-disease in Coton de Tulear breed, a mutation c.996G>A in AGXT gene was found. At the protein level, the glycine amino acid is substituted with serine in position 102 (Vidgren et al. 2012). The presence of mutation c.996G>A was tested in 118 Finnish dogs of Coton de Tulear breed. A heterozygous mutation was found in 8.5 % animals, i.e. carriers of PH-disease without clinical signs. This preliminary study reported PH as a cause of neonatal death in Coton de Tulear puppies and recommended genetic testing of breeding dogs before mating to prevent the birth of puppies affected with PH I (Vidgren et al. 2012).  

The PH I disease in Coton de Tulear is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P (positive / positive) genotype only. The dogs with P/N (positive /negative) genotype are clinically without any symptom. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

References:
Vidgren G., Vainio-Siukola K., Honkasalo S., Dillard K, Anttila M., Vauhkonen H.: Primary hyperoxaluria in Coton de Tulear. Animal Genetics, 2012

Jansen J.H. & Arnesen K. (1990) Oxalate nephropathy in a Tibetan spaniel litter. A probable case of primary hyperoxaluria. Journal of Comparative Pathology 103, 79-84.

Danpure C.J., Jennings P.R. & Jansen J.H. (1991) Enzymological characterization of a putative canine analogue of primary hyperoxaluria type 1. Biochimica Biophysica Acta 1096, 134-8.

Goldstein R.E., Narala S., Sabet N., Goldstein O. & McDonough S.P.(2009) Primary hyperoxaluria in cats is caused by a mutation in the feline GRHPR gene. Journal of Heredity 100, S2-7.

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Usual turnaround time: 7 business days
1 test price: 54.00 $ without VAT