Leukocyte adhesion deficiency type I in a mixed-breed dog

• Published in: Journal of veterinary diagnostic investigation 2013-03, Vol.25 (2), p.291-296
• Main Authors: Zimmerman, Kurt L, McMillan, Kate, Monroe, WIlliam E, Sponenberg, D. Phillip, Evans, Nick, Makris, Melissa, Hammond, Sarah H, Mullarky, Isis Kanevsky, Boudreaux, Mary K
• Format: Article
• Language: English
• Subjects: adhesion; Anaplasma; anemia; Animals; Anti-Bacterial Agents - therapeutic use; bacteria; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Bacterial Infections - veterinary; biopsy; Borrelia; Canine distemper virus; chemistry; Dog Diseases - diagnosis; Dog Diseases - pathology; Dogs; Ehrlichia; fever; flow cytometry; genes; granulocyte colony-stimulating factor; Hepatozoon; inflammation; leukemia; Leukocyte-Adhesion Deficiency Syndrome - diagnosis; Leukocyte-Adhesion Deficiency Syndrome - pathology; Leukocyte-Adhesion Deficiency Syndrome - veterinary; Male; missense mutation; Mycobacterium; Mycoplasma; neutrophils; pathogens; polymerase chain reaction; toxicity
• ISSN: 1040-6387; 1943-4936
• DOI: 10.1177/1040638713478814

A 6-month-old, neutered male, mixed-breed dog was examined for a 2-month persistent fever, nonhealing dermal metacarpal area wound, and leukocytosis (47.0-198.0 × 10(3)/μl). Serum chemistry findings included hypoalbuminemia, hyperglobulinemia, hyperphosphatemia, and hyperphosphatasemia. Complete blood cell count results revealed a moderate microcytic, hypochromic nonregenerative anemia with a profound leukocytosis (198.5 × 10(3)/μl), characterized by neutrophilia with toxicity and hypersegmentation, and significant band cells. Tick-borne disease titers (genera Anaplasma, Ehrlichia, and Borrelia) were negative, as were polymerase chain reaction for other infectious agents (genera Hepatozoon, Mycobacterium, Mycoplasma; and Canine distemper virus). No agents were identified in a deep dermal biopsy (conventional and special histochemical stains) of the chronic draining, metacarpal region lesion. Cytology of the draining tract revealed numerous mixed bacteria and a surprising lack of neutrophils. Chronic occult blood loss with iron deficiency was considered a possible cause of the anemia. Differentials for the leukon were chronic established inflammation (occult infectious agent), chronic neutrophilic leukemia, paraneoplastic leukocytosis (neoplastic source of granulocyte colony-stimulating factor [CSF] or granulocyte-macrophage CSF), and leukocyte adhesion deficiency (LAD). The possibility of a LAD disorder was further investigated because of the noted hypersegmented neutrophils, absence of neutrophils in the cytology sample, the animal’s young age, and persistence of clinical and laboratory signs. Flow cytometry of blood neutrophils showed a 60% reduction in surface expression of the β2-integrin (CD18) subunit, whereas neutrophil function tests (oxidative burst and phagocytosis) were normal. Genetic testing revealed a homozygous missense mutation in the β2-integrin subunit gene, previously recognized only in purebred Irish Setters, leading to a diagnosis of LAD type 1 disorder in this mixed-breed dog.