Genetic basis of Hyperoxaluria GRHPR (Primary Hyperoxaluria Type II) - in cats is an autosomal recessive genetic disorder caused by mutations in the GRHPR gene. This gene encodes the enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which normally converts glyoxylate to glycolate, preventing the accumulation of toxic oxalate. The known mutation in cats is a splice site mutation (G>A) at intron 4 of the GRHPR gene causing exon 5 skipping, frameshift, and a premature stop codon in the protein. Cats must inherit two defective copies of the gene (homozygous) to develop the disease; carriers with one copy are asymptomatic but can pass the mutation to offspring.
Pathophysiology - The GRHPR enzyme deficiency disrupts the normal metabolism of glyoxylate, leading to increased levels of oxalate in the blood. Oxalate precipitates as calcium oxalate crystals, primarily in the renal tubules, leading to kidney damage. This results in acute kidney failure characterized by crystal deposition and renal tissue injury. The accumulation of oxalate crystals may also contribute to neurological signs through motor neuron denervation and muscle atrophy.
Complications - Acute onset kidney failure in young cats, typically appearing between 3 to 5 months of age. Clinical signs include anorexia, dehydration, weakness. Calcium oxalate crystal deposition in the kidneys causing nephrolithiasis and nephrosis. Recurrent urinary tract symptoms and crystal-related kidney damage. Neurological symptoms due to motor neuron involvement and muscle atrophy. Without intervention, the disease often progresses rapidly and is fatal.
Why This Matters to Breeders and Vets - Genetic Testing: DNA tests for the GRHPR mutation allow identification of carriers and affected cats, helping breeders avoid producing affected kittens through informed mating decisions. Early Diagnosis: Awareness of hyperoxaluria symptoms assists veterinarians in distinguishing the disease from toxicities like ethylene glycol poisoning. Breed Management: Recognizing the autosomal recessive inheritance supports breeding programs to reduce the frequency of this lethal condition, particularly in breeds like Domestic Shorthair and Burmese. Welfare Impact: Early detection facilitates better clinical management and humane care for cats afflicted by this rapidly progressive renal disease.
Summary - Hyperoxaluria GRHPR in Domestic Short Hair and other breeds is a severe autosomal recessive metabolic disorder caused by a splice site mutation in the GRHPR gene leading to enzyme deficiency. This results in toxic oxalate buildup and calcium oxalate crystal deposition in the kidneys, causing acute kidney failure, neurological complications, and early mortality. Genetic testing and responsible breeding practices are essential to control this fatal disease and improve feline health outcomes. Veterinary awareness ensures accurate diagnosis and appropriate care for affected cats.