Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) is an autoinflammatory disease (previously designated lazy leukocyte syndrome) characterized by defective leukocyte mobility, abnormal adaptive immunity, and symptoms and signs of autoinflammation.

PFIT mutation has been characterized in 7 families with 13 affected individuals of Northern European, Qatari, Pakistani, Turkish, and Syrian lineage. Males and females are equally affected, and the inheritance pattern is autosomal recessive. The genetic defect stems from missense mutations in the actin regulatory gene WD repeat protein 1 (WDR1), which encodes actin-interacting protein 1 (AIP1), a protein that regulates the actin cytoskeleton.

The mutated WDR1 also activates caspase-1, which leads to autoinflammation due to excessive interleukin-18 (IL-18) production by monocytes. These mutations also disrupt the actin cytoskeleton to impact both innate and adaptive immunity, as neutrophil, monocyte / macrophage, B cell, and T cell functions are impaired, resulting in a primary immunodeficiency.

Affected individuals usually exhibit signs in infancy and early childhood and often have decreased life expectancy, although some patients begin to show disease manifestations during their second decade of life.

Clinical features include early onset of recurrent respiratory infections with cough, pneumonia, bronchiectasis, rhinitis, cutaneous infections, stomatitis, otitis media, gingivitis, and fevers. Infections usually arise from bacterial organisms such as Staphylococcus aureus, Streptococcus pneumoniae, Pneumocystis jiroveci, Haemophilus influenzae, Escherichia coli, and Enterococcus, and may result in severe viral infections, including varicella. Patients can have microstomia, oral stenosis, perianal ulceration, hypertrichosis, nodulocystic acne, and generalized poor wound healing.

Some patients demonstrate the predominant clinical picture of innate immunity defect with impaired neutrophil function and severe neutrophilia. Others experience periodic fevers that may last 3-7 days and recur every 6-12 weeks and immunodeficiency, although sometimes without neutropenia / lymphopenia and instead with leukocytosis, chronic thrombocytopenia, and anemia. Lastly, a third distinct profile is characterized with a mostly impaired adaptive immune system, manifesting with profound B-cell lymphopenia and dysfunction and mild defects in T-cell activation. Patients often show poor growth and mild to moderate intellectual disability, although some patients demonstrate normal growth and development.