Related gene: DOCK2
Inheritance pattern: Autosomal recessive
DOCK2 deficiency is an autosomal recessive disorder associated with early-onset invasive bacterial and viral infections, lymphopenia, and defective T, B, and NK cell function. DOCK2 protein is important not only for the cytoskeletal structure of peripheral blood leukocytes but also for thymus, spleen, and liver function. DOCK2 deficiency causes defective actin polymerization and migration in T, B, and NK cells, impaired NK cell killing ability, and diminished cytokine (interferon) production in peripheral blood mononuclear cells in response to viral infections with consequent increase in viral replication.
Most known individuals with DOCK2 deficiency presented in the first four months of life with recurrent viral and bacterial respiratory tract infections, as well as chronic diarrhea and failure to thrive. Affected individuals may be susceptible to disseminated vaccine-strain varicella, oral thrush, and severe infections with nontuberculous mycobacteria, human herpesvirus-6, mumps, parainfluenza virus, adenovirus, cytomegalovirus (CMV), and Klebsiella pneumoniae. Additional clinical features include thrombocytopenia, hepatomegaly, and colitis. Treatment with interferons is under investigation, while hematopoietic stem cell transplantation (HSCT) may be curative for the disease.