XANT type 2c – XANTHINURIA type II (2c)

Description:  Xanthinuria is a hereditary metabolic disease caused by the presence of an excessive amount of xanthine in the urine. Xanthine is a by-product of the metabolic breakdown of nucleic acid purines into uric acid. Because of its low solubility, xanthine can precipitate in the urine, which increases the risk of xanthine urinary or kidney stone formation and can cause serious kidney disease.

Hereditary xanthinuria results from mutations either in the coding sequence for xanthine dehydrogenase (XDH, xantinuria type 1) or in the coding sequence for molybdenum cofactorsulfurase (MOCOS, xanthinuria type 2). Xanthine dehydrogenase (XDH) is an enzyme in the purine metabolic pathway that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. Molybdenum cofactorsulfurase (MOCOS) converts the molybdenum cofactor XDH from the oxo form to the sulfide form, which is essential for XDH activity. Individuals with xanthinuria type I have XDH variants that lead to XDH deficiency, while individuals with xanthinuria type II have MOCOS variants that result in both MOCOS and XDH deficiencies. Clinically, the subtypes of hereditary xanthinuria are indistinguishable.

So far, different variants have been identified that cause hereditary xanthinuria:

Type 1: mixed breed XDH c.654G > A

Type 2a: English Toy Terrier / Manchester Terrier (Type 2a) MOCOS c.232G > T

Type 2b: English Cocker Spaniel and Cavalier King Charles Spaniel MOCOS p.Ala128Glyfs*30

Type 2c: in dachshunds (all types) MOCOS p.Leu46Pro

Inheritance: autosomal recessive

Mutation:  c.137T > C (p.Leu46Pro) in MOCOS gene

Sample: EDTA whole blood (1.0 ml) or 2 buccal brushes. For official purposes, the confirmation of the dog’s identity by Veterinarian is recommended.

The analysis is suitable for the following breeds: Dachshund all types

Notes: Sanger sequencing of [candidate genes] XDH and MOCOS identified four putative causal variants … : an XDH c.654G > A splice site variant that results in skipping of exon 8 (mixed-breed dog), a MOCOS c.232G > T splice site variant that results in skipping of exon 2 (Manchester Terriers), a MOCOS p.Leu46Pro missense variant (Dachshund), and a MOCOS p.Ala128Glyfs*30 frameshift variant that results in a premature stop codon (Cavalier King Charles Spaniels and English Cocker Spaniel)