Immundeficiency 40 D84.8

Very rare, autosomal recessive primary form of combined immunodeficiency (CID) that mainly affects the number and function of T cells. Furthermore, other more variable defects in the function of B cells and NK cells are found. Patients experience severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation (Dobbs et al. 2015).

It is caused by an autosomal recessive mutation in the DOCK2 gene.

Sharifinejad N et al (2021) reported a case of a 27-month-old girl with recurrent prneumonia and a history of skeletal tuberculosis at 19 months of age. Her immunologic examination revealed persistent lymphopenia and a low count of CD4 + T cells along with elevated levels of CD19 +, CD20 +, CD16 +, and CD56 + cells. She also had a high immunoglobulin (Ig)-E level and a slightly reduced IgM level with a nonprotective antibody titer to diphtheria.

Whole-exome sequencing (WES) revealed a homozygous frameshift deletion mutation (c.1512delG, p.I505Sfs*28) in exon 16 of the DOCK2 gene.

The literature search revealed 14 patients with DOCK2 deficiency who suffered from both cellular and humoral immunodeficiencies leading to early-onset infections, particularly human herpesvirus (HHV) infections.

1. Dobbs K et al (2015) Inherited DOCK2 deficiency in patients with early-onset invasive infections. New Eng J Med 372: 2409-2422.
2. Sharifinejad N et al (2021) First patient in the Iranian Registry with novel DOCK2 gene mutation, presenting with skeletal tuberculosis, and review of literature. Allergy Asthma Clin Immunol 17:126.