Erstmaliger Nachweis des SLC2A9:p.C188F Gendefekts bei einem Deutschen Jagdterrier mit Ammoniumurat-Urolithiasis

Zusammenfassung

Ein 1,5-jähriger, männlich intakter Deutscher Jagdterrier wurde erstmalig 2018 mit Hämaturie vorstellig. In einer abdominalen Ultraschalluntersuchung wurden multiple hyperechogene Strukturen in der Harnblase festgestellt. Eine Urinuntersuchung wies auf eine hochgradige Ammoniumurat- oder Xanthin-Kristallurie hin. Erst nach einer Zystotomie und einer Harnsteinanalyse konnte 2019 eine Ammoniumurat-Urolithiasis diagnostiziert werden. Der Patient wurde homozygot für die SLC2A9:p.C188F Variante, welche in eine hochgradige Hyperurikämie und Hyperurikosurie resultiert, getestet. Diese Kasuistik berichtet über den ersten publizierten Fall eines Deutschen Jagdterriers, bei dem die SLC2A9:p.C188F Variante nachgewiesen wurde. Die Leserschaft soll dafür sensibilisiert werden, dass dieser Gendefekt auch in anderen Rassen als Dalmatinern auftreten kann.

Abstract

A 1,5-year-old intact male German Hunting Terrier was initially presented 2018 with hematuria. An abdominal ultrasound revealed multiple hyperechogenic structures in the urinary bladder. A urinalysis indicated severe crystalluria (ammonium urate or xanthine). Following cystotomy and urinary calculus analysis, ammonium urate urolithiasis was diagnosed in 2019. The patient was tested homozygous at the SLC2A9:p.C188F variant, which results in severe hyperuricemia and hyperuricosuria. This case report presents the first incidence of the SLC2A9:p.C188F gene variant being detected in a German Hunting Terrier. Veterinary practitioners are encouraged to consider the possibility of this gene defect presenting in breeds beyond the Dalmatian.

Schlüsselwörter

Hyperurikosurie (HUU) - Harnstein - SLC2A9-Gendefekt - Hund

Keywords

Hyperurikosuria (HUU) - urinary calculus - SLC2A9 gene defect - dog

Publication History

Received: 17 September 2023

Accepted: 01 March 2024

Article published online:
22 August 2024

• Literatur

• 1 Nakanishi T, Ohya K, Shimada S. et al. Functional cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in renal reabsorption of urate. Nephrol Dial Transplant 2013; 28: 603-611 DOI: 10.1093/ndt/gfs574.
• 2 Maiuolo J, Oppedisano F, Gratteri S. et al. Regulation of uric acid metabolism and excretion. Int J Cardiol 2016; 213: 8-14 DOI: 10.1016/j.ijcard.2015.08.109.
• 3 Alford A, Furrow E, Borofsky M. et al. Animal models of naturally occurring stone disease. Nat Rev Urol 2020; 17: 691-705 DOI: 10.1038/s41585-020-00387-4.
• 4 Lulich JP, Berent AC, Adams LG. et al. ACVIM Small Animal Consensus Recommendations on the Treatment and Prevention of Uroliths in Dogs and Cats. J Vet Intern Med 2016; 30: 1564-1574 DOI: 10.1111/jvim.14559.
• 5 Mandal AK, Mount DB. The molecular physiology of uric acid homeostasis. Annu Rev Physiol 2015; 77: 323-345 DOI: 10.1146/annurev-physiol-021113-170343.
• 6 McCue J, Langston C, Palma D. et al. Urate Urolithiasis. Compendium: Continuing Education for Veterinarians 2009; 468-475
• 7 Hyndman D, Liu S, Miner JN. Urate Handling in the Human Body. Curr Rheumatol Rep 2016; 18: 34 DOI: 10.1007/s11926-016-0587-7.
• 8 Adomako E, Moe OW. Uric Acid and Urate in Urolithiasis: The Innocent Bystander, Instigator, and Perpetrator. Semin Nephrol 2020; 40: 564-573 DOI: 10.1016/j.semnephrol.2020.12.003.
• 9 Breu D, Stieger N, Muller E. Occurrence of uroliths – age-, breed-, and gender-specific differences in dogs from Germany. Tierarztl Prax Ausg K Kleintiere Heimtiere 2021; 49: 6-12 DOI: 10.1055/a-1334-0733.
• 10 Villaverde C. Urate bei Erkrankungen der Harnblase. Veterinary Focus 2014; 24 n°1: 10-14
• 11 Bartges JW, Callens AJ. Urolithiasis. Vet Clin North Am Small Anim Pract 2015; 45: 747-768 DOI: 10.1016/j.cvsm.2015.03.001.
• 12 Bartges JW, Osborne CA, Lulich JP. et al Canine urate urolithiasis. Etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 1999; 29: 161-191 xii–xiii DOI: 10.1016/s0195-5616(99)50010-7.
• 13 Kopecny L, Palm CA, Segev G. et al. Urolithiasis in dogs: Evaluation of trends in urolith composition and risk factors (2006-2018). J Vet Intern Med 2021; 35: 1406-1415 DOI: 10.1111/jvim.16114.
• 14 Roe K, Pratt A, Lulich J. et al. Analysis of 14,008 uroliths from dogs in the UK over a 10-year period. J Small Anim Pract 2012; 53: 634-640 DOI: 10.1111/j.1748-5827.2012.01275.x.
• 15 Houston DM, Moore AE, Favrin MG. et al. Canine urolithiasis: a look at over 16 000 urolith submissions to the Canadian Veterinary Urolith Centre from February 1998 to April 2003. Can Vet J 2004; 45: 225-230
• 16 Cosgrove L, Hammond G, McLauchlan G. Primary portal vein hypoplasia and SLC2A9 mutation associated with urate urolithiasis in a Spanish water dog. Can Vet J 2015; 56: 1153-1157
• 17 Bannasch D, Safra N, Young A. et al. Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. PLoS Genet 2008; 4: e1000246 DOI: 10.1371/journal.pgen.1000246.
• 18 Karmi N, Safra N, Young A. et al. Validation of a urine test and characterization of the putative genetic mutation for hyperuricosuria in Bulldogs and Black Russian Terriers. Am J Vet Res 2010; 71: 909-914 DOI: 10.2460/ajvr.71.8.909.
• 19 Karmi N, Brown EA, Hughes SS. et al. Estimated frequency of the canine hyperuricosuria mutation in different dog breeds. J Vet Intern Med 2010; 24: 1337-1342 DOI: 10.1111/j.1939-1676.2010.0631.x.
• 20 Meadows JRS, Kidd JM, Wang GD. et al. Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 2023; 24: 187 DOI: 10.1186/s13059-023-03023-7.
• 21 Donner J, Anderson H, Davison S. et al. Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs. PLoS Genet 2018; 14: e1007361 DOI: 10.1371/journal.pgen.1007361.
• 22 Konstantinidis AO, Patsikas MN, Papazoglou LG. et al. Congenital Portosystemic Shunts in Dogs and Cats: Classification, Pathophysiology, Clinical Presentation and Diagnosis. Vet Sci 2023; 10 DOI: 10.3390/vetsci10020160.
• 23 Bannasch D, Henthorn PS. Changing paradigms in diagnosis of inherited defects associated with urolithiasis. Vet Clin North Am Small Anim Pract 2009; 39: 111-125 DOI: 10.1016/j.cvsm.2008.09.006.
• 24 Nelson NC, Nelson LL. Anatomy of extrahepatic portosystemic shunts in dogs as determined by computed tomography angiography. Vet Radiol Ultrasound 2011; 52: 498-506 DOI: 10.1111/j.1740-8261.2011.01827.x.
• 25 Raskin RE, Murray KA, Levy JK. Comparison of home monitoring methods for feline urine pH measurement. Vet Clin Pathol 2002; 31: 51-55 DOI: 10.1111/j.1939-165x.2002.tb00279.x.
• 26 Westropp JL, Larsen JA, Johnson EG. et al. Evaluation of dogs with genetic hyperuricosuria and urate urolithiasis consuming a purine restricted diet: a pilot study. BMC Vet Res 2017; 13: 45 DOI: 10.1186/s12917-017-0958-y.