Hereditary xanthinuria is an autosomal recessive genetic disorder that results in excessive xanthine (a metabolic byproduct) in the urine. This increases the risk for formation of xanthine bladder or kidney stones and can cause significant kidney disease. Hereditary xanthinuria is a result of mutations in either xanthine dehydrogenase (XDH, type 1 xanthinuria) or molybdenum cofactor sulfurase (MOCOS, type 2 xanthinuria). Xanthinuria can also occur from non-genetic factors such as exposure to drugs that inhibit XDH (e.g. allopurinol). This is termed iatrogenic xanthinuria.
Who gets it?
Hereditary xanthinuria is rare but has been reported in multiple breeds. In the past 5 years, the Minnesota Urolith Center received xanthine stone submissions from dogs of the following breeds with suspected hereditary xanthinuria: Cavalier King Charles Spaniel, Toy Manchester Terrier, Dachshund, English Cocker Spaniel, Chihuahua, and mixed breed dogs.
To date, we have identified causative mutations in a mixed breed dog (Type 1a), Toy Manchester Terriers (Type 2a), and English Cocker Spaniels & Cavalier King Charles Spaniels (Type 2b). For Toy Manchester Terriers, we recommend the Type 2a test, and for English Cocker Spaniels and Cavalier King Charles Spaniels, we recommend the Type 2b test. If you are submitting a sample from any other breed, we recommend running all three tests. Genetic test results can be used to help guide medical management of affected dogs, identify dogs at risk even before they form stones, and to inform breeding decisions.
What are the clinical signs?
Xanthinuria leads to the development of urinary stones. This causes irritation that may manifest as straining to urinate, frequent urination, urgency with urination, blood in the urine, or life-threatening urinary obstructions. Microscopic crystals can also accumulate in the kidney and cause kidney disease. Patients with xanthinuria can present at virtually any age from a few months onwards. Though many patients have serious consequences, some remain asymptomatic. Males appear to be more likely to form stones than females.
How is it managed?
Once diagnosed, stones can be treated surgically or with other removal techniques, but the disease tends to recur without additional intervention. High fluid intake is important, along with a low purine diet. Therapeutic veterinary low purine diets are available by prescription. Egg, nuts, and dairy are generally low purine sources of protein; foods with high purine content such as liver, kidney, bacon, and most seafood should be avoided.