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Characterization of aminoaciduria and hypoaminoacidemia in dogs with hepatocutaneous syndrome

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  • 1 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 3 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 5 Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 6 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 7 Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 8 MedVet New Orleans, 1937 Veterans Memorial Blvd, Metairie, LA 70005.
  • | 9 Mid-Atlantic Animal Specialty Hospital, 4135 Old Town Rd, Huntingtown, MD 20639.
  • | 10 Heart's Ease Veterinary Care, 827 E Washington St, Louisville, KY 40206.
  • | 11 Vista Veterinary Specialists, 7425 Greenhaven Dr, Sacramento, CA 95831.
  • | 12 Red Bank Veterinary Hospital, 197 Hance Ave, Tinton Falls, NJ 07724.
  • | 13 Oradell Animal Hospital, 580 Winters Ave, Paramus, NJ 07652.
  • | 14 Animal Clinic of Union, 540 US-50 Union, MO 63084.
  • | 15 Essex Animal Hospital, 355 Talbot St N, Essex, ON N8M 2W3, Canada.
  • | 16 Edmonton Holistic Veterinary Clinic, 8215 102 St, Edmonton, AB T5A 0A7, Canada.
  • | 17 Blue Pearl Grand Rapids, 1425 Michigan St NE, Ste F, Grand Rapids, MI 49503.
  • | 18 Basking Ridge Animal Hospital, 340 S Finley Ave, Basking Ridge, NJ 07920.
  • | 19 Westport Animal Hospital, 814 Post Rd E, Westport, CT 06880.
  • | 20 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

Abstract

OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS).

ANIMALS 20 client-owned dogs of various breeds and ages.

PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2). Amino acid concentrations in heparinized plasma and urine (samples obtained within 8 hours of each other) were measured by use of ion exchange chromatography. Urine creatinine concentration was used to normalize urine amino acid concentrations. Plasma amino acid values were compared relative to mean reference values; urine-corrected amino acid values were compared relative to maximal reference values.

RESULTS All dogs had generalized hypoaminoacidemia, with numerous amino acid concentrations < 50% of mean reference values. The most consistent and severe abnormalities involved glutamine, proline, cysteine, and hydroxyproline, and all dogs had marked lysinuria. Urine amino acids exceeding maximum reference values (value > 1.0) included lysine, 1-methylhistidine, and proline.

CONCLUSIONS AND CLINICAL RELEVANCE Hypoaminoacidemia in dogs with HCS prominently involved amino acids associated with the urea cycle and synthesis of glutathione and collagen. Marked lysinuria and prolinuria implicated dysfunction of specific amino acid transporters and wasting of amino acids essential for collagen synthesis. These findings may provide a means for tailoring nutritional support and for facilitating HCS diagnosis.

Abstract

OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS).

ANIMALS 20 client-owned dogs of various breeds and ages.

PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2). Amino acid concentrations in heparinized plasma and urine (samples obtained within 8 hours of each other) were measured by use of ion exchange chromatography. Urine creatinine concentration was used to normalize urine amino acid concentrations. Plasma amino acid values were compared relative to mean reference values; urine-corrected amino acid values were compared relative to maximal reference values.

RESULTS All dogs had generalized hypoaminoacidemia, with numerous amino acid concentrations < 50% of mean reference values. The most consistent and severe abnormalities involved glutamine, proline, cysteine, and hydroxyproline, and all dogs had marked lysinuria. Urine amino acids exceeding maximum reference values (value > 1.0) included lysine, 1-methylhistidine, and proline.

CONCLUSIONS AND CLINICAL RELEVANCE Hypoaminoacidemia in dogs with HCS prominently involved amino acids associated with the urea cycle and synthesis of glutathione and collagen. Marked lysinuria and prolinuria implicated dysfunction of specific amino acid transporters and wasting of amino acids essential for collagen synthesis. These findings may provide a means for tailoring nutritional support and for facilitating HCS diagnosis.

Contributor Notes

Dr. Bechtold's present address is Dogs and Cats Veterinary Referral and Emergency, 6700 Laurel-Bowie Rd, Bowie, MD 20715.

Address correspondence to Dr. Center (sac6@cornell.edu).