Hereditary xanthinuria in a goat

Krystal J. Vail, Nicole M. Tate, Tasha Likavec, Katie M. Minor, Philippa M. Gibbons, Raquel R. Rech, Eva Furrow

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

A 2-year-old mixed breed goat was presented for a 1-day history of anorexia and 1 week of weight loss. Serum biochemistry disclosed severe azotemia. Abdominal ultrasound examination showed decreased renal corticomedullary distinction, poor visualization of the renal pelves, and dilated ureters. On necropsy, the kidneys were small, the pelves were dilated, and the medulla was partially effaced by variably sized yellow nephroliths. Histologically, cortical and medullary tubules were distended by yellow-brown, multilayered crystals. Stone composition was 100% xanthine. Exonic sequencing of xanthine dehydrogenase (XDH) and molybdenum cofactor sulfurase (MOCOS) identified 2 putative pathogenic variants: a heterozygous XDH p.Leu128Pro variant and a homozygous MOCOS p.Asp303Gly variant. Variant frequencies were determined in 7 herd mates, 12 goats undergoing necropsy, and 443 goats from genome databases. The XDH variant was not present in any of these 462 goats. The MOCOS variant allele frequency was 0.03 overall, with 3 homozygotes detected. Hereditary xanthinuria is a recessive disorder in other species, but the XDH variant could be causal if the case goat is a compound heterozygote harboring a second variant in a regulatory region not analyzed or if the combination of the XDH and MOCOS variants together abolish XDH activity. Alternatively, the MOCOS variant alone could be causal despite the presence of other homozygotes, because hereditary xanthinuria in humans often is asymptomatic. Ours is the first report describing the clinical presentation and pathology associated with xanthine urolithiasis in a goat. The data support hereditary xanthinuria, but functional studies are needed to conclusively determine the causal variant(s).

Original languageEnglish (US)
Pages (from-to)1009-1014
Number of pages6
JournalJournal of veterinary internal medicine
Volume33
Issue number2
DOIs
StatePublished - Mar 1 2019

Bibliographical note

Funding Information:
We gratefully acknowledge the Minnesota Urolith Center for nephrolith identification, and the Texas A&M University VTPB histopathology laboratory for technical expertise. We thank Gwenola Tosser-Klopp, the leader of the VarGoats project, and the other VarGoats contributors for sharing variant calls for XDH and MOCOS. Partial support for EF was provided by an NIH ORIP K01 Mentored Research Scientist Development Award (K01-OD019912).

Funding Information:
We gratefully acknowledge the Minnesota Urolith Center for nephrolith identification, and the Texas A&M University VTPB histopathology laboratory for technical expertise. We thank Gwenola Tosser-Klopp, the leader of the VarGoats project, and the other VarGoats contributors for sharing variant calls for XDH and MOCOS. Partial support for EF was provided by an NIH ORIP K01 Mentored Research Scientist Development Award (K01-OD019912). This work was presented as a poster at the 2017 annual meeting of the American College of Veterinary Pathologists.

Publisher Copyright:
© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Keywords

  • MOCOS
  • caprine
  • kidney
  • urinary system
  • urolith
  • xanthine

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