Cystinuria
Cystinuria is observed in many dog breeds, but is clinically evident in only a few.
The cause is a metabolic disorder caused by defects in the genes SLC3A1 and/or SLC7A9. These are responsible for amino acid transport; if they are defective due to mutations, the concentration of the amino acids cystine, ornithine, lysine and arginine ('COLA' amino acids) increases in the urine.
The poorly soluble cystine forms urinary stones. Symptoms of stone formation are: Blood in the urine, colic and even kidney failure.
As a result of the anatomical and hormonal conditions, often only the males are affected.
Cystinuria type 1
occurs in Newfoundlands, Landseers and Labrador Retrievers.
In Newfoundlands and Landseers, a mutation (C663T) in the SLC3A1 gene leads to loss of function. The mode of inheritance is autosomal recessive. In affected dogs, massive COLA uria and stone formation occur before sexual maturity.
In Labrador Retrievers, the causative mutation (c.350delG) is in exon 1 of the SLC3A1 gene. The mode of inheritance is also autosomal recessive. However, the mutation is rare. The test can help to differentiate the mutation in clinically manifest cystinuria and to identify possible carriers.
Cystinuria type 2
These are the forms in which autosomal dominant inheritance occurs, but the clinical presentation is milder than in animals affected by Type I.
Type II-A in Australian Cattle Dogs, mutation: SLC3A1:c.1095_1100delACCACC, autosomal dominant.
Type II-B in Miniature Pinschers, mutation: SLC7A9:c.964G>A, autosomal dominant.