Hyperuricosuria (HUU) in Dogs: The Uric Acid Gene and Which Breeds Carry It
Urate stones are painful, recurrent, and sometimes life-threatening — and they are largely preventable through DNA testing
Hyperuricosuria (HUU) is a genetic condition that causes abnormally high levels of uric acid in the urine, leading to the formation of urate bladder stones (urolithiasis). Dogs with HUU excrete uric acid rather than breaking it down further into allantoin as most dogs do. The resulting crystals can form stones that obstruct the urinary tract — a painful and potentially dangerous condition that may require surgery.
What Is HUU and What Causes It?
In most mammals — including most dogs — uric acid is converted to allantoin by an enzyme called uricase (encoded by the UOX gene). Allantoin is highly soluble and easily excreted in urine without forming crystals.
In HUU-affected dogs, a mutation in the SLC2A9 gene disrupts uric acid transport, causing abnormal accumulation in the blood and urine. Because uric acid is poorly soluble, it precipitates in the urine and forms ammonium urate crystals and stones.
Important note: Dalmatians are a special case. All purebred Dalmatians are homozygous for a different form of uric acid excretion disorder (caused by a different gene). HUU testing for the SLC2A9 mutation is separate from Dalmatian-specific testing.
Signs of HUU in Affected Dogs
- Frequent urination, straining to urinate
- Blood in urine (hematuria)
- Recurrent urinary tract infections
- Urinary obstruction — particularly dangerous in male dogs, where the urethra is narrower
- Vomiting and lethargy if obstruction is complete
- Recurrent stone formation even after surgical removal or dietary management
Male dogs are much more commonly diagnosed because their anatomy makes obstruction more likely. Females may carry HUU and form stones but obstruct less frequently.
Breeds With Known HUU Prevalence
The SLC2A9 mutation has been identified in numerous breeds:
- Black Russian Terriers — High prevalence
- South African Boerboels
- Bulldogs (English)
- American Staffordshire Terriers
- Weimaraners
- German Shepherd Dogs
- Giant Schnauzers
- Siberian Huskies
- Jack Russell Terriers (Parson Russell Terriers)
- Australian Shepherds
- Labrador Retrievers
And many others. The mutation has spread across breeds through crosses and common ancestry. Any breed with unknown HUU prevalence should be checked if urate stones have been identified in the line.
Genetics and Inheritance
HUU follows autosomal recessive inheritance:
- Clear (N/N) — No copies of the mutation. Will not develop HUU. Cannot pass the mutation.
- Carrier (N/HUU) — One copy. Uric acid metabolism is normal or near-normal. Not expected to form urate stones. Can pass the mutation to 50% of offspring.
- Affected (HUU/HUU) — Two copies. High uric acid levels in urine. High risk of forming urate stones.
DNA Testing for HUU
DNA tests for HUU are available from:
- Paw Print Genetics
- Embark (included in comprehensive panels)
- Animal Genetics
- UC Davis Veterinary Genetics Lab
Testing is inexpensive and straightforward — a cheek swab sample is all that is needed.
Breeding Decisions
| Parent 1 | Parent 2 | Expected Offspring |
|---|---|---|
| Clear | Clear | All clear — no HUU |
| Clear | Carrier | 50% clear, 50% carriers — no affected |
| Carrier | Carrier | 25% clear, 50% carriers, 25% affected |
| Clear | Affected | All carriers — no affected |
| Carrier | Affected | 50% carriers, 50% affected |
Goal: Never produce affected (HUU/HUU) offspring. Breed Clear to Clear, or at minimum Clear to Carrier.
Management of HUU-Affected Dogs
Affected dogs that develop stones can be managed but require ongoing veterinary attention:
- Diet — Low-purine diets reduce uric acid production. Avoid organ meats, sardines, and other high-purine foods.
- Hydration — Maintaining high water intake dilutes urine and reduces stone formation risk
- Medication — Allopurinol blocks uric acid production but must be used carefully (it can cause xanthine stones if combined with a high-purine diet)
- Monitoring — Regular urinalysis and ultrasound to detect stone formation early
- Surgery — Stones may require surgical removal or lithotripsy
Prevention through DNA testing is far preferable to the ongoing management required for an affected dog.
Summary
Hyperuricosuria is caused by an SLC2A9 mutation that prevents proper uric acid breakdown, leading to urate stone formation. It is autosomal recessive — two copies are required for the disease. Carriers are typically unaffected. DNA testing accurately identifies Clear, Carrier, and Affected dogs. Breed Clear to Clear or Clear to Carrier to prevent affected offspring. Test all breeding dogs in at-risk breeds — treatment of urate stones is expensive, recurring, and in some cases life-threatening.