Cystinuria, type II-A

 

Gene: SLC3A1

Transmission: Autosomal dominant

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Deletion, SLC3A1 gene: c1098_1103 del.ACCACG, p.(T367_T368del)

Medical system: Renal

Breeds: Akita, American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Australian Kelpie, Border Collie, Boxer, Labrador Retriever, Pembroke Welsh Corgi, Siberian Husky

Age of onset of symptoms:

Cystinuria is a genetic metabolic disease affecting the reabsorption of the amino acid cystine by the proximal tubules of the kidneys. The SLCA1 and SLC7A9 genes code for a protein complex found in kidney epithelial cells that functions to transport cystine among several other amino acids.    Both recessive and dominant mutations can occur in either of these genes such that cystine cannot be recovered and resulting in increased concentrations of cystine in the urine.  Since cystine has a low solubility in water, high concentrations of cystine can cause crystals and stones to form within the urinary tract.  Affected animals may present with difficulty urinating, frequent urination in small quantities (stranguria), the presence of blood in the urine (hematuria), and increased cystine in the urine (cystinuria). The presence of stones in the urinary tract can lead to secondary bacterial infections.   If the stones block the urethra, a potentially life-threatening medical crisis can occure involving severe abdominal pain, vomiting, renal failure, and possible bladder rupture. At risk males will develop symptoms earlier than females, due to the different anatomy of their urinary systems.  In animals known to be susceptible to cystinuria it is important to avoid dehydration and follow a suitable diet to prevent cystine crystal formation.  DNA tests are available and should be used to reduce the frequency of the mutations involved.

The classification and naming of canine cystinurias, as suggested by Brons et al. (2013), is based on the transmission (Type I for recessive, Type 2 for dominant) and the gene that is mutated (-A for the SLC3A1 gene, -B for the SLC7A9 gene), as follows:

Cystinuria Type I-A : Type I = recessive, -A = SLC3A1 gene

Cystinuria Type II-A : Type II = dominant, -A = SLC3A1 gene

Cystinuria Type I-B : Type I = recessive, -B = SLC7A9 gene

Cystinuria Type II-B : Type II = dominant, -B = SLC7A9 gene

 

References:

OMIA link: [1879-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Fitzwilliams T, Wolff-Sneedorff, JL, Fredholm M, et al. (2023) Evaluation of the value of genetic testing for cystinuria in the Danish population of English bulldogs. Anim Genet 54(4):566-569.  [pubmed/36971195]

Kovaříková S, Maršálek P, Vrbová K. (2021) Cystinuria in dogs and cats: What do we know after almost 200 years? Animals (Basel) 11:2437.  [pubmed/34438894]

Brons AK, Henthorn PS, Raj K, et al. (2013) SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system. J Vet Intern Med 27:1400-8. [pubmed/24001348]

Henthorn PS, Liu J, Gidalevich T, et al. (2000) Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs. Hum Genet. 107(4):295-303. [pubmed/11129328]

Casal ML, Giger U, Bovee KC, Patterson DF. (1995) Inheritance of cystinuria and renal defect in Newfoundlands. J Am Vet Med Assoc. 207(12):1585-9. [pubmed/493896]

 

Contributed by: Lea Minogue and Amélie Poirier, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).