DOCK 8 IMMUNODEFICIENCY

Abstract

Autosomal recessive (AR) DOCK8 deciency is a well-known actinopathy, a combined primary immune deciency with impaired actin polymerization that results in altered cell mobility and immune synapse. DOCK8-decient patients present early in life with eczema, viral cutaneous infections, chronic mucocutaneous candidiasis, bacterial pneumonia and abscesses, together with eosinophilia, thrombocytosis, lymphopenia, and variable dysgammaglobulinemia that usually includes Hyper-IgE. In fact, before its genetic aetiology was known, patients were described as having a form of Hyper-IgE syndrome, a name now deprecated in favour of genetic defects. We describe a school-age female patient with a clinical picture suggestive of DOCK8 deciency, except for high serum IgE or a family history: early onset, failure to thrive, oral fungating lesion, generalized maculopapular rashes, bronchiolitis, pneumonia, recurrent otitis media, bronchiectasis, candidiasis, leucocytosis, eosinophilia, high IgA, low IgG and low CD4+ T cells. We were able to conrm the diagnosis through protein expression and whole-exome sequencing. We review the clinical, laboratory, and genetic features of 200 DOCK8-decient patients. Despite this, the constellation of signs, symptoms, and ndings allow the suspicion of DOCK8 deciency and other actinopathies.