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Canine Primary Hyperoxaluria Type I (PH I)
| Acronym: | PH I |
| Gene: | AGXT |
| Mutation: | c.304G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Canine primary hyperoxaluria type I (PH I) is a rare, inherited disorder of glyoxylate metabolism affecting the Coton Tulear dog breed. PH I is a form of a wider group of primary hyperoxalurias, which are known to affect humans, dogs, and cats. Hyperoxaluria is a condition in which oxalate concentrations in the urine are extremely high, which causes kidney damage. Primary hyperoxaluria is a disease caused by a genetic mutation, in which the liver produces too much oxalate. Primary hyperoxalurias consist of three main types, each associated with specific metabolic defects. From them, type I is the most common and most severe one with a rapid progression. 80% of cases of primary hyperoxaluria are caused by Type I, which has an early age of onset.
Oxalate is a small molecule naturally present in the human or animal body from food intake or as an end product of metabolism reactions, such as the metabolism of certain proteins or the metabolism of vitamin C. However, oxalate is not used within the body for anything, nor degraded, so it needs to be excreted through the urine or feces. In the bladder, oxalate can bind with calcium and form insoluble crystals, which are the most common cause of kidney stones in human patients (75%). Stones can be renal and bladder and they may cause a secondary infection of urine, urinary obstruction, and kidney damage, all followed by severe and acute pain. Oxalate deposits may develop in the bones, joints, and bone marrow. In severe cases, primary hyperoxaluria type I may cause anemia and thrombocytopenia.
In affected dogs, symptoms occur at age of 3 to 4 weeks in form of sudden illness causing inappetence, vomiting, lethargy, decreased urine production, abdominal pain, blood in the urine, and death. After the development of the first symptoms, in a time frame of 2 months affected dogs die or get euthanized due to humane reasons. The necropsy reveals numerous oxalate crystals present in the tubules in the renal cortex and at the corticomedullary junction. The causative mutation of the primary hyperoxaluria type I (PH I) in Coton de Tulears is in the AGXT gene. Canine primary hyperoxaluria type I (PH I) is inherited as an autosomal recessive disorder. A dog carrying one copy of the mutated gene is heterozygous and will not show the PH I symptoms. When mating two carriers (heterozygotes) at conception each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Vidgren G, Vainio-Siukola K, Honkasalo S, Dillard K, Anttila M, Vauhkonen H.: Primary hyperoxaluria in Coton de Tulear. Anim Genet. 2012 Jun; 43(3):356-61.