Abstract
Cystinuria is caused by hereditary defects in the renal basic amino acid transporter. The lack of appropriate resorption leads to varied losses of cystine, ornithine, lysine, and arginine; however, it is the insolubility of cystine in acid urine which leads to cystine crystalluria and urolithiasis. Cystinuria has been reported in humans, many canine breeds, and several cats.3 Cystinuria and cystine uroliths have also been reported in a captive caracal (Caracal caracal, formerly Felis caracal)5 and captive and free-ranging maned wolves (Chrysocyon brachyurus).1,2 In humans, cystinuria is inherited as an autosomal recessive trait. Similarly, an autosomal recessive mode of transmission has been documented in Newfoundland dogs with severe cystinuria due to a missense mutation in the rBAT gene.3,4 A diagnosis of cystinuria can be made based upon a urinary nitroprusside screening test, the presence of hexagonal cystine crystals in urine sediment, urolith crystal analysis, and urinary amino acid analysis (Josephine Deubler Genetic Disease Testing Laboratory (PennGen) at the University of Pennsylvania).
We report here on two captive male servals (Leptailurus serval) with obstructive cystine urolithiasis, as well as the urinary nitroprusside test results on a captive serval population at the same facility (n=24). Clinically affected servals were 16 and 4 yr old; the first was the grand sire of the second serval. Both presented with a brief history of anorexia and acute signs of urinary obstruction. Radiographically, cystic calculi were identified as radio-opaque structures in the urethra. During surgery it was noted that the bladder was ruptured in one case and severely inflamed in the second. There were numerous calculi in the bladder and urethra (50–100). The calculi were yellow brown in color and ranged between 2 and 5 mm in size. Based upon crystallographic analysis the calculi contained purely cystine. Surgical correction was attempted in the second case (perineal urethrostomy). However, intraoperative findings and serum biochemistry results indicated a poor prognosis for these two animals and euthanasia was elected. All the servals at the facility are maintained on the same diet (fresh/frozen rodents) and water ad libitum.
Furthermore, the urine of several related servals kept in the same facility tested positive for cystine by the nitroprusside test, but have not developed any calculi based upon radiographs and clinical observation. As dietary measures seem not to be rewarding in other species, emphasis on diuresis, alkalinizing, and chelation may be considered in cystinuric servals.
Cystinuria and cystine calculi should be included as a differential diagnosis for servals with urinary tract problems. Further studies are needed to define the renal transport defect and mode of inheritance. It is important to determine the heritability of diseases since heritable diseases are a key factor in captive breeding programs.
Acknowledgments
Supported in part by a grant from the National Institutes of Health (RR #002512).
Literature Cited
1. Bovee, K.C., M. Bush, J. Dietz, P. Jezyk, and S. Segal. 1981. Cystinuria in the maned wolf. Science. 212:919–920.
2. Bush, M. and K.C. Bovee. 1978. Cystinuria in a maned wolf. J. Am. Vet. Med. Assoc. 173:1159–1162.
3. Casal, M.L., U. Giger, K.C. Bovee, et al. 1995. Inheritance of cystinuria and renal defect in Newfoundlands. J. Am. Vet. Med. Assoc. 217:1585–1589.
4. Henthorn, P.S., J. Liu, T. Gidalevich, J. Fang, M. Casal, P.D. Patterson, and U. Giger. 2000. Polymorphism and disease-causing mutation in rBAT gene: an animal model for type I cystinuria. Hum. Genet. 107:295– 303.
5. Jackson, O.F. and D.M. Jones. 1979. Cystine calculi in a caracal lynx (Felis caracal). J. Comp. Path. 89:39–42.