Hyperuricosuria (SLC2A9 gene)

Hyperuricosuria and hyperuricemia (HUU) is a disorder characterized by the formation of urate stones or crystals in the urinary tract, causing painful urination and bleeding.

Symptoms

HUU manifests in dogs with symptoms such as increased frequency of urination, painful urination, blood in the urine, abdominal pain, vomiting and decreased appetite. Males are more susceptible to developing fatal urethral obstruction. It is essential to be alert to any signs of HUU in dogs and seek veterinary care immediately if HUU is suspected.

Disease Management

Treatment of HUU in dogs usually consists of a combination of dietary changes and medication to reduce uric acid levels in the urine. To achieve this, a low-purine diet that reduces uric acid production in the body is recommended. In severe cases, surgery may be necessary to remove urinary stones.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Hyperuricosuria and hyperuricemia in dogs are characterized by the formation of urate crystals or stones in the urinary tract. It has been identified that the SLC2A9 gene, classified as a member of the glucose transporter family, also functions as a urate transporter in humans and possibly in dogs. A specific mutation (c.563G>T) in the fifth transmembrane domain of the protein causes an amino acid substitution (Cys188Phe) at a highly conserved residue. This change can disrupt the function of the protein and affect urate transport. This variant is found in homozygosity in all Dalmatian dogs, although its allele frequency is lower in other breeds.

Most affected breeds

American Staffordshire Terrier
Australian Shepherd
Black Russian Terrier
Boerboel
Dalmatian
English Bulldog
German Shepherd Dog
Giant Schnauzer
Labrador
Parson Russell Terrier
Pomeranian
Spanish water dog
Weimaraner

Bibliography

Bannasch D, Safra N, Young A,et al. Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. PLoS Genet. 2008 Nov;4(11):e1000246.