Molecular test for hereditary xanthinuria type II, an inborn error of purine metabolism due to a deficiency of molybdenum cofactor sulfurase (MOCOS) that produces xanthine accumulation and xanthine urolithiasis. It affects the metabolic system and manifests clinically as renal/urinary urolithiasis. The test reports clear/carrier/affected status for the corresponding variant.

Applicable breeds: Cavalier King Charles Spaniel, Dachshund, English Toy Terrier, Manchester Terrier and English Cocker Spaniel. Carrier frequencies are not published systematically (limited data).

- Xanthine urolithiasis (radiolucent stones)\n- Haematuria and dysuria\n- Renal colic and urinary obstruction (more frequent in males)\n- Renal failure in cases of prolonged obstruction\n- Hyperxanthinuria in urine/plasma

Hereditary xanthinuria is classified into two types: type I, due to a deficiency of xanthine dehydrogenase/oxidase, and type II, due to a deficiency of molybdenum cofactor sulfurase (MOCOS), which inactivates both xanthine oxidase and aldehyde oxidase. The canine form has been associated with variants in the MOCOS gene in several breeds, characterised molecularly by Tate and colleagues in 2021.

- Genotype breeding animals before mating\n- Do not mate carrier×carrier (25% risk of affected homozygotes); carrier×clear produces 0% affected and 50% carriers\n- An affected animal must not be bred; a carrier may be mated to a clear animal without producing affected offspring\n- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer

Confirmation by stone analysis (xanthine), biochemistry (elevated xanthinuria/xanthinaemia) and molecular testing. Differentiate from urolithiasis of other compositions (struvite, oxalate, urate) and from xanthinuria secondary to allopurinol (a drug that raises xanthine). Dietary management (low in purines, high hydration), limited urinary alkalinisation (xanthine is more soluble in an acid medium than urate) and monitoring of renal function.

1. Tate NM, Minor KM, Lulich JP, Mickelson JR. Multiple variants in XDH and MOCOS underlie xanthine urolithiasis in dogs. Mol Genet Metab Rep 29:100792, 2021. PMID: 34584846
2. OMIA:001819-9615. Xanthinuria, type II in Canis lupus familiaris. https://omia.org/OMIA001819/9615/
3. OMIA:002445-9615. Xanthinuria, type I in Canis lupus familiaris. https://omia.org/OMIA002445/9615/