Xanthinurea, type 1

Gene: XDH

Transmission: Autosomal, probably recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, XDH gene; c.2042C>T, p.(Ala681Val), chromosome A3.

Breeds: Domestic Cat, Maine Coon, Persian

Medical system: Urinary

Age of onset of symptoms: From 3 to 8 months of age.

Uroliths are of clinical importance in the cat as they are a major cause of feline urinary tract obstruction.  Uroliths can have various chemical compositions;  uroliths derived from purine metabolism, which are relatively uncommon, can be urate based or xanthine based.  Xanthine is an intermediate product of purine metabolism to uric acid.  When this metabolism is disrupted by genetic mutations, an accumulation of xanthine can occur in the urine, resulting in xanthinuria, xanthine uroliths, and the potential for urinary tract obstruction.  Two genetic lesions are recognized that can result in xanthinuria, including xanthinuria type I, with mutations of the XDH gene and resulting in a defective xanthine dehydrogenase enzyme, and xanthinuria type II, with mutations in the MOCOS gene resulting in a defective molybdenum cofactor sulfurase enzyme.

The clinical signs xanthinuria in cats vary according to the accumulation of xanthine crystals in the urinary tract and kidneys. Affected animals may present urinary symptoms such as blood in the urine (hematuria), difficulty urinating (stranguria), excessive urinary frequency (pollakiuria) or urinary urgency. These signs are often associated with urinary obstructions, which can be particularly serious and potentially fatal. In addition, xanthine crystals can accumulate in the kidneys, causing acute renal failure. Some cats may also become lethargic and lose their appetite, often due to the discomfort associated with urinary obstructions or renal dysfunction. Although many affected cats present severe symptoms, some remain asymptomatic until the onset of more significant renal obstruction or deterioration.

An 8-month-old domestic shorthaired cat was presented with frequent and difficult urination.  Lab analysis revealed multiple small uroliths in the urine.  A DNA analysis revealed a homozygous mutation within the XDH gene, consistent with a diagnosis of Xanthinurea type I.  A survey of 340 cats established a carrier frequency of 26.6% for the mutation and included homozygous animals within the Maine Coon and Persian breeds.  True frequencies of the mutation for the Maine Coon and Persian breeds await further studies.

The characterized mutation in the XDH gene was not found in other cases of xanthuria in cats, including a pedigree of Munchkin cats and an unrelated domestic cat.  This suggests that other unresolved genetic factors may also be the cause of xanthinuria in cats.

References:

OMIA link: [2445-9685]

Pritchard EC, Haase B, Wall MJ, et al. (2024) Xanthinuria in a familial group of Munchkin cats and an unrelated domestic shorthair cat. J Feline Med Surg 26:1098612X241241408. [pm/38771789]

Pritchard E, Samaha G, Mizzi K, Boland L. (2023) Candidate causative variant for xanthinuria in a Domestic Shorthair cat. Anim Genet 54:576-580.  [pm/36970934]

Contributed by: Laurie-Anne Dault and Ouiam Guissous, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)