Hereditary defect of leukocyte integrins and platelet function due to kindlin-3 deficiency. It produces a combined phenotype of immunodeficiency (recurrent infections due to failure of leukocyte adhesion and migration) and haemorrhagic diathesis (defective platelet activation). It has been described in the German Shepherd and the Rottweiler, and is inherited in an autosomal recessive manner.

Described in the German Shepherd. It is a rare disease; no reliable carrier frequencies are published in the general population.

- Recurrent bacterial infections from the earliest stage\n- Leukocytosis with neutrophils that do not migrate to tissues\n- Haemorrhagic tendency: prolonged bleeding after trauma or surgery\n- Growth retardation\n- Poor prognosis without intensive management

The canine form, described in the German Shepherd, is analogous to human LAD-III and is caused by mutations in the FERMT3 gene (kindlin-3), a protein that regulates integrin activation in leukocytes and platelets. Boudreaux and collaborators (2010) identified in an affected German Shepherd a 12-base-pair insertion in the coding region of KINDLIN3 (now FERMT3), which inserts four amino acids (RRLP) into the kindlin-3 homology domain and is associated with a higher risk of bleeding and susceptibility to infections. The variant has also been documented in the Rottweiler (OMIA 001525-9615).

- Test breeding animals from lines with a history before mating\n- Do not mate two carriers: 25% risk of affected homozygotes\n- A carrier may be mated to a clear animal; test the offspring intended for breeding\n- Avoid spreading the allele to lines where it is absent\n- In case of doubtful results, supplement with a functional leukocyte and platelet study

Differential diagnosis with CLAD (ITGB2/CD18), with primary thrombopathies and with secondary immunodeficiencies. The combination of recurrent infections, persistent leukocytosis and bleeding is highly suggestive. The canine molecular basis is established (FERMT3, OMIA 001525-9615) and is analogous to human LAD-III.

1. Boudreaux MK et al. (2010) A mutation in the canine Kindlin-3 gene associated with increased bleeding risk and susceptibility to infections. Thromb Haemost 103(2):475-477. PMID: 20126836
2. Hugo TB, Heading KL (2014) Leucocyte adhesion deficiency III in a mixed-breed dog. Aust Vet J 92(8):299-302. PMID: 24954630
3. OMIA:001525-9615. Leukocyte adhesion deficiency, type III in Canis lupus familiaris. https://omia.org/OMIA001525/9615/