Common variable immunodeficiency-13 D84.1

Immunodeficiency 13 and IKZF1 defect (CVID13) is an autosomal dominant inherited chronic immunodeficiency syndrome caused by a heterozygous mutation in the IKZF1 gene (603023) on chromosome 7p12. Immunodeficiency 13 is characterized clinically by recurrent bacterial infections, primarily affecting the respiratory tract, and is associated with hypogammaglobulinemia and decreased B-cell counts. There is no increased susceptibility to fungal or viral infections in this immunodeficiency.

The age at onset of clinical features can range from infancy to adulthood, and some patients may have a mild disorder or even remain clinically asymptomatic (S. Kuehn et al. 2016).

Hypogammaglobulinemia, decreased number of B cells. Bone marrow aspirates may show a marked decrease in pro-B cells and early progenitor cells, indicating incomplete blockade of B cell differentiation.

B-cell acute lymphoblastic leukemia (Kuehn et al. 2016).

Goldman et al (2012) reported a male infant who was born preterm at 33 weeks' gestation and showed pancytopenia at birth. During the last week of gestation, there was severe polyhydramnios and moderate fetal hydrops. The patient had anemia requiring transfusions, lymphopenia with decreased granulocytes, and thrombocytopenia. Bone marrow aspiration showed bone marrow aplasia with absent myelopoiesis. Laboratory studies revealed the absence of circulating B cells, minimal numbers of NK cells, and an abundance of T lymphocytes.

Kuehn et al (2016) reported 29 individuals from six unrelated families with CVID13. Subjects from the families were first evaluated for immunodeficiencies between the ages of 3 and 32 years after recurrent or severe bacterial infections, often by Streptococcus pneumoniae. All had hypogammaglobulinemia and decreased B-cell counts. Subsequently, other affected family members were identified: most had recurrent infections associated with hypogammaglobulinemia, although some were not clinically affected. None had evidence of increased susceptibility to fungal or viral infections. Examination of antibodies to vaccine antigens in 8 patients revealed that 6 patients had no antibody formation, 1 patient had progressive loss of antibody, and 1 patient had a normal titer. In almost all patients, the number of CD19+ B cells was severely reduced, although memory B cells were present. Several patients had an increase in CD8+ T cells with an inverted CD4:CD8 ratio.

1. Georgopoulos K et al (1994) The Ikaros gene is required for the development of all lymphoid lineages. Cell 79: 143-156.
2. Goldman FD et al (2012) Congenital pancytopenia and absence of B lymphocytes in a neonate with a mutation in the Ikaros gene. Pediat Blood Cancer 58: 591-597.
3. Kuehn HS et al (2016) Loss of B cells in patients with heterozygous mutations in IKAROS. New Eng J Med 374: 1032-1043.