Cystinuria Type IA

Cystinuria type IA is an inherited disease caused by a mutation in the SLC3A1 gene, which encodes the rBAT protein, essential for the transport of amino acids such as cystine in the kidney and intestine. This mutation causes a defect in cystine reabsorption, resulting in the formation of crystals and uroliths in the urinary tract.

Symptoms

Clinical signs usually appear after 2 months of age. The main feature is the formation of cystine crystals and uroliths in the urinary tract. Affected cats may experience difficulty urinating, blood in the urine, increased urinary frequency and, in severe cases, lower urinary tract obstruction and renal failure. In addition to these urinary symptoms, some cats may exhibit lethargy, excessive salivation and seizures due to accumulation of ammonia in the body, a complication associated with cystinuria.

Disease Management

The management of cystinuria focuses on the elimination, dissolution or prevention of urolith formation through dietary changes and medical treatment. A diet low in protein, methionine and cystine, with a high water content is recommended.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, 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 cat 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 cats carrying genetic variants that may cause disease is not recommended, even if they do not show symptoms.

Technical report

Cystinuria type IA in cats is an inherited metabolic disease that affects the renal transport of amino acids such as cystine. In this condition, a mutation is observed in the SLC3A1 gene, which encodes the rBAT protein essential for the amino acid transporter system. This protein is expressed in the apical membrane of the epithelial cells of the renal proximal tubule and small intestine facilitating the transport of amino acids such as cystine from the lumen of the renal tubule and intestine into the epithelial cells. The specific mutation identified in cystinuric cats, c.1342C>T, leads to a substitution of a highly conserved arginine residue for tryptophan at position p.Arg448Trp of rBAT. This variant affects the structure and function of rBAT, promoting the formation of cystine uroliths in the lower urinary tract of affected cats.

Most affected breeds

Domestic Shorthair

Bibliography

Mizukami K, Raj K, Giger U. Feline cystinuria caused by a missense mutation in the SLC3A1 gene. J Vet Intern Med. 2015 Jan