Abstract
BackgroundDedicator of cytokinesis 2 (DOCK2) deficiency is an inborn error of immunity characterized by cellular and humoral immunological abnormalities leading to early-onset infections.Case presentationWe reported a novel case of a 27 months old girl presenting with recurrent pneumonia and a history of skeletal tuberculosis at the age of 19-month-old. Her immunological workup revealed persistent lymphopenia and low CD4 + T cell count along with elevated levels of CD19 +, CD20 +, CD16 +, and CD56 + cells. Furthermore, she had a high level of immunoglobulin (Ig) E and a slightly reduced IgM level with a non-protective antibody titer against diphtheria. The whole-exome sequencing (WES) analysis identified a homozygous frameshift deletion mutation (c.1512delG, p.I505Sfs*28) in exon 16 of the DOCK2 gene. We also conducted electronic searches in PubMed, Web of Science, and Scopus databases and reviewed the articles reporting patients with DOCK2 deficiency. The literature search yielded 14 DOCK2-deficient patients suffering from both cellular and humoral immune defects leading to early-onset infections, particularly human herpesvirus (HHV) infection.ConclusionDOCK2 deficiency should be considered in the context of severe or unusual early-onset infections, especially HHV infections, in a patient with a probable clinical diagnosis of combined immunodeficiency. We also recommended that DOCK2-deficient patients might benefit from T-cell receptor excision circle (TREC) assay as part of the routine newborn screening program.
Highlights
Dedicator of cytokinesis 2 (DOCK2) is a subfamily of guanine exchange factors required for the activation of intercellular GTPases and subsequent release of adenosine triphosphate (ATP) in response to various stimuli [1]
DOCK2 deficiency should be considered in the context of severe or unusual early-onset infections, especially human herpesvirus (HHV) infections, in a patient with a probable clinical diagnosis of combined immunodeficiency
We recommended that DOCK2-deficient patients might benefit from T-cell receptor excision circle (TREC) assay as part of the routine newborn screening program
Summary
DOCK2 deficiency should be contemplated in the context of severe or unusual early-onset infections, especially HHV infections, accompanied by laboratory data indicating both cellular and humoral defects. Decreased CD4 + T cell count was the most prevalent immunological abnormality detected in these patients. The role of the newborn TREC screening program in detecting suspected patients with DOCK2 deficiency needs to be clarified in the upcoming studies. Abbreviations DOCK2: Dedicator of cytokinesis 2; Ig: Immunoglobulin; HHV: Human herpes virus; NK: Natural killer; ATP: Adenosine triphosphate; ROS: Reactive oxygen species; CID: Combined immunodeficiency; PIDTC: Primary immunodeficiency treatment consortium; MTB: Mycobacterium tuberculosis; TRECs: T cell receptor excision circles; PHA: Phytohemagglutinin; HSCT: Hematopoietic stem cell transplantation; SCID: Severe combined immunodeficiency; WES: Whole-exome sequencing; PICU: Pediatric intensive care unit; CMV: Cytomegalovirus
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