Canine Leukocyte Adhesion Deficiency type 3

This hereditary blood disease mainly affects German Shepherds and causes an increased risk of infections and bleeding.

Symptoms

Affected dogs have impaired blood clotting and immune system functions may be impaired. Affected German Shepherds may have lameness, recurrent skin infections, osteomyelitis or bone infections and gingivitis. Most dogs can live for years, although their life expectancy is reduced as they are more at risk for severe infections or excessive bleeding due to accidental injury or during a surgical procedure.

Disease Management

Veterinarians should be informed of dogs with this deficiency prior to any surgical intervention. Should your dog show any symptoms, you should see your veterinarian for evaluation.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

In FERMT3 gene, leading to abnormal expression of kindlin-3. This cytoplasmic protein is highly expressed in leukocytes and platelets, and acts as an important regulator of blood coagulation and leukocyte adhesion. Here we analyzed whether or not the mutation c.1349_1350insAAGACGGCTGCC is present, which results in the insertion of several nucleotides in the FERMT3 gene sequence and was discovered in German shepherds. This mutation causes platelets to take longer to aggregate and form clots so there is an increased risk of severe bleeding and also results in altered leukocyte function which makes affected dogs more susceptible to recurrent infections, especially in the skin, bones and gums.

Most affected breeds

German Shepherd Dog

Bibliography

Boudreaux MK, Wardrop KJ, Kiklevich V,et al. A mutation in the canine Kindlin-3 gene associated with increased bleeding risk and susceptibility to infections. Thromb Haemost. 2010 Feb;103(2):475-7.

Cortese L, Christopherson PW, Pelagalli A. Platelet Function and Therapeutic Applications in Dogs: Current Status and Future Prospects. Animals (Basel). 2020 Jan 25;10(2):201.

Hugo TB, Heading KL. Leucocyte adhesion deficiency III in a mixed-breed dog. Aust Vet J. 2014 Aug;92(8):299-302.