Cystinuria is an inherited disorder caused by a defect in the transport of cystine, an amino acid, in the kidney tubules. This defect has been linked to a gene called SLC3A1 in the Newfoundland breed. Normally, cystine that is filtered in the kidney is reabsorbed within the tubules, resulting in little cystine in the urine. Dogs with Cystinuria do not properly reabsorb cystine (and a few other amino acids) in the kidney tubules, causing the urine to contain abnormally high levels of cystine. Cystine is insoluble in neutral pH or acidic urine, so excess urinary cystine results in formation of cystine crystals, which in turn can lead to formation of cystine calculi (stones) in the kidney and/or bladder.
Because males have long, narrow urethras compared to females, irritation and blockage by calculi is much more common in the male. Males with Cystinuria suffer repeated inflammations of the urinary tract and are at risk for urinary blockage, which can, if not treated promptly, lead to kidney failure, bladder rupture, and death. Cystinuria has been reported in many breeds (and mixed breeds) of dogs. Although Newfoundlands are not the breed most commonly associated with cystinuria, Newfoundlands are at an increased risk of developing cystine calculi formation compared to most other breeds. The average age of onset of clinical signs attributable to Cystinuria in other dog breeds is about 4.8 years, but in Newfoundlands, signs appear as early as 6 months to 1 year, suggesting that the Newfoundland breed suffers from a more severe form of the disorder than do other breeds. Recurrence of calculi following surgical removal also occurs much more rapidly in Newfoundlands than in other breeds.
Canine Cystinuria disease in Newfoundlands shows an autosomal recessive mode of inheritance; therefore two copies of the defective gene, one inherited from each parent, have to be present for a dog to be affected by the disease. Dogs with one copy of the defective gene and one copy of the normal gene - called carriers - show no symptoms but can pass the defective gene onto their offspring.
Canine Cystinuria is typically diagnosed through the identification of characteristic crystals in the urine. Cystine can be identified in the urine of an affected dog in as early as 2 days of age using a nitroprusside spot test or paper chromatography; either of these tests can be used to further confirm a suspected case of Cystinuria. While the nitroprusside spot test can detect affected dogs, it will not determine whether a dog carries a gene for Cystinuria. A dog carrying only one copy of the mutated cystinuria gene (carrier) would display no symptoms of disease, but could potentially produce affected offspring if bred to another carrier or affected dog. Until recently, the nitroprusside spot test was the only available means of testing for Cystinuria. A DNA-based diagnostic test for the detection of Canine Cystinuria in Newfoundlands is now available. This test employs the latest advances in DNA technology to specifically target the gene associated with this disease, ensuring 100% accuracy of detection. This DNA test can definitively diagnose affected animals, as well as carriers of the mutated gene. By selectively identifying carriers of Cystinuria, breeders can effectively remove these animals from their breeding programs and eventually eradicate this disease from their lines.