Genetic basis of Dihydroxyadenine urolithiasis Type IA in dogs - is caused by a mutation in the adenine phosphoribosyltransferase (APRT) gene. The specific mutation identified is a missense mutation c.260G>A (p.Arg87Gln) in the APRT gene, which leads to loss of enzyme function and accumulation of insoluble 2,8-dihydroxyadenine in the urinary tract. The condition is inherited in an autosomal recessive manner, meaning affected dogs will have two copies of the defective gene. Carriers with one copy do not show symptoms but can pass the mutation to offspring
Pathophysiology - APRT deficiency impairs purine metabolism, resulting in excessive levels of 2,8-DHA, which crystallizes in the urinary tract and forms stones. These stones cause urinary obstruction, inflammation, and kidney damage, leading to symptoms such as frequent urination, blood in urine, pain, and potential acute kidney injury or chronic kidney disease. The uroliths are radiolucent and require specific diagnostic techniques for detection.
Complications - Urinary tract obstruction causing pain and potential life-threatening urinary retention. Recurring urolith formation with associated kidney infections. Progressive kidney damage and potential renal failure with delayed or inadequate treatment.
Why This Matters to Breeders and Vets - Early genetic testing and diagnosis enable preventive breeding strategies to avoid producing affected puppies. Veterinarians can diagnose and manage the condition with appropriate interventions such as stone removal surgery, dietary management, and medications like xanthine dehydrogenase inhibitors (e.g., allopurinol) to reduce stone formation and kidney damage. Genetic knowledge informs prognosis and improves patient outcomes by guiding lifelong care.
