Genetic basis - Caused by a single base pair insertion mutation in the AP3B1 gene (adaptor protein complex 3, beta subunit 1) located on canine chromosome 3. The mutation creates a frameshift and premature stop codon, preventing production of functional AP3 beta protein. The syndrome is inherited in an autosomal recessive pattern; affected dogs have two copies of the mutation, carriers have one copy without symptoms.
Pathophysiology - The AP3 complex mediates intracellular trafficking of proteins to lysosomes and granules in neutrophils and other cells. Mutation causes absence or dysfunction of the AP3 beta subunit, leading to deficient neutrophil elastase delivery, accumulation of inactive precursors, and impaired neutrophil function. This results in cyclic fluctuations of blood cells, especially neutrophils, leading to periods of profound neutropenia (very low neutrophil count). Neutropenia cycles approx. every 11-14 days, lasting 5-6 days with increased infections risk.
Complications - Clinical signs begin early in life (often within first few weeks). Symptoms include recurrent bacterial infections, fever, anorexia, stunted growth, bleeding, hypopigmented (diluted gray) coat, and eye abnormalities. Severe neutropenia episodes increase susceptibility to life-threatening infections. Most affected puppies have shortened lifespan, with some dying within weeks of birth.
Why This Matters to Breeders and Vets - For breeders, identifying carriers and affected dogs prevents breeding lifethreatening hematopoietic disorders and improves breed health. Veterinarians use genetic testing to aid early diagnosis, treatment planning, and managing infections. Understanding the inheritance pattern guides breeders in making sound breeding decisions. Early diagnosis and supportive care can extend affected dogs' quality of life.