Xanthinuria is a rare genetic disorder in dogs, with some instances reported in Toy Manchester Terriers and English Toy Terriers. It causes excessive Xanthine (a naturally occurring by-product of purine metabolism) in the urine which can lead to kidney stones, kidney disease, and urinary obstructions.
- Symptoms of Xanthinuria
- Diagnosis & Treatment
- Genetic Inheritance of Xanthinuria
- DNA Testing for Xanthinuria
1. Symptoms of Xanthinuria
Xanthinuria leads to the development of urinary stones. This causes irritation that may manifest as straining to urinate, frequent urination, urgency with urination, recurring urinary tract infections, blood in the urine, abdominal cramping and pain, or life-threatening urinary obstructions.
Microscopic crystals can also accumulate in the kidney and cause kidney disease. Dogs with xanthinuria can present at virtually any age from a few months onwards. Though many have serious consequences, some remain asymptomatic. Males appear to be more likely to form stones than females.
Always consult a vet if you suspect your dog is affected by Xanthinuria.
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2. Diagnosis & Treatment
A qualified vet may use a combination of diagnostic tests including blood tests, urinalysis, ultrasound, x-rays, and urolith (urinary stone) analysis.
There is no specific cure for Xanthinuria. Urinary stones may be removed surgically or with other removal techniques, but the disease tends to recur without additional intervention.
Ongoing management may include ensuring that the dog has a high fluid intake along with a low purine diet (available by prescription). A qualified vet should work with the owner to set out a management plan for an affected dog. Therapeutic veterinary low purine diets are available by prescription.
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3. Genetic Inheritance of Xanthinuria
Xanthinuria is a rare autosomal recessive genetic disorder that has been reported in a small number of breeds including the Toy Manchester Terrier and English Toy Terrier.
Xanthinuria can also occur from non-genetic factors such as exposure to drugs that inhibit XDH (e.g. allopurinol). This is termed iatrogenic xanthinuria. Hereditary xanthinuria is a result of mutations in either xanthine dehydrogenase (XDH, type 1 xanthinuria) or molybdenum cofactor sulfurase (MOCOS, type 2 xanthinuria).
Toy Manchester Terriers and English Toy Terriers are affected by Xanthinuria type 2a (XU2a).
For a dog to be affected, both parents must be carriers. Mating a carrier of Xanthinuria (XU2a) to a dog that tests clear does not produce progeny affected by Xanthinuria although the progeny may themselves be carriers
DNA testing for Xanthinuria of the sire and dam is essential to inform mating decisions. Two carriers should not be mated together. Prospective puppy owners should always ask for evidence of the results of Xanthinuria on the sire and dam.
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4. DNA Testing for Xanthinuria
DNA testing is available to identify whether a dog is a carrier of Xanthinuria. Each of the three Xanthinuria tests screen for a specific DNA mutation in a specific gene. These mutations are all inherited in an autosomal recessive manner. Typically, the test requires a straightforward swab taken from inside the cheek.
Test kits can be ordered through:
Both of these testing providers can also test for Juvenile Dilated Cardiomyopathy (JDCM) and Von Willebrand’s Disease (vWD). We recommend that all breeders carry out DNA tests for JCDM and Xanthinuria on potential sires and dams, as well as having Patella Luxation Tests as a minimum.
Carriers of Xanthinuria (XU2a) should not be bred to other carriers and mated only to partners who have tested clear of JDCM. While Xanthinuria in English Toy Terriers is rare, it is essential for our vulnerable and numerically small breed that breeders use Xanthinuria testing to inform breeding decisions to avoid producing Xanthinuria affected dogs.
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Interpreting Test Results
- ‘D’ indicates the deleterious (Xanthinuria) form of the gene
- ‘N’ indicates the normal form of the gene.
A dog’s particular combination of N or D forms of the gene is known as its genotype.
Clear (N/N):
Clear dogs have no copies of the mutation and cannot pass the mutation on to offspring. However, this test result does not rule out the possibility that a dog could be affected or a carrier for a different xanthinuria mutation.
Carrier (D/N):
A carrier dog has only one copy of the mutation. Since the mutation is recessive, one copy will not cause xanthinuria and risk for xanthine stones. Carriers will, on average, pass the mutation on to half of their offspring. This does not mean that they need to be taken out of the breeding pool, but they should be bred to clear dogs to avoid producing affected puppies.
Affected (D/D):
An affected dog has two copies of the mutation that causes xanthinuria (this is also referred to as being homozygous affected). They will pass on a copy of the mutation to all of their offspring, but if bred to clear dogs, the offspring will only be carriers. Many, but not all, dogs with xanthinuria will go on to form urinary stones and/or kidney disease. Signs can start at virtually any age from a few months onwards. Urinary stones cause irritation that may manifest as straining to urinate, frequent urination, urgency with urination, blood in the urine, or life-threatening urinary obstructions. If kidney damage is present, signs may manifest as excessive
thirst and urination.
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Breeding Outcomes
- Clear (N/N) x Clear (N/N) = 100% Clear (N/N)
- Clear (N/N) x Carrier (D/N) = 50% Clear (N/N), 50% Carrier (D/N)
(This is an average, individual litters may see anywhere from 100% Clear to 100% Carrier) - Clear (N/N) x Affected (D/D) = 100% Carrier (D/N)
- Carrier (D/N) x Carrier (D/N) = 25% Clear (N/N), 50% Carrier (D/N), 25% Affected (D/D)
(This is an average, individual litters may see more or less of any result) - Carrier (D/N) x Affected (D/D) = 50% Carrier (D/N), 50% Affected (D/D)
(This is an average, individual litters may see anywhere from 100% Carrier to 100% Affected) - Affected (D/D) x Affected (D/D) = 100% Affected (D/D)
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Submission of Xanthinuria Test Results
DNA testing for Xanthinuria is one of the ETT Club and The Kennel Club’s recommended tests for the English Toy Terrier (B&T).
All DNA tests carried out through Laboklin will automatically be submitted to the Royal Kennel Club on your behalf.
Scanned copies or photographs of the DNA results certificate from the University of Minnesota should be emailed to health.results@thekennelclub.org.uk
In order to strengthen and build the DNA database for the English Toy Terrier (B&T) please send all historical results to: health.results@thekennelclub.org.uk photographs or scanned copies of the certificates accepted.
All results submitted, whether automatically through Laboklin or sent by the breeder/owner directly to the RKC, will be logged and added to the RKC’s Health Test Results Finder.
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