Common variable immunodeficiency (CVID) is a rare diagnosis characterized by low levels of serum IgG, low serum IgA and/or IgM, and failure to produce specific protective antibody titers. This condition can present clinically as recurrent infections and/or inflammatory and hematologic complications. CVID is a complex condition that may not have a singular genetic cause; however, multiple genes have been implicated. Correlation between genetic testing, clinical presentation, and laboratory findings is vital in guiding diagnosis and treatment. We present a single case of an infant with recurrent infections, low IgG, and a pathogenic variant on genetic testing associated with CVID.
A 7-month-old female born at 35 weeks with a complex medical history, including 14q partial deletion syndrome, was admitted to the ICU for respiratory failure and sepsis from methicillin-susceptible Staphylococcus aureus pneumonia. Her hospital course was complicated by recurrent bacterial infections, including ventilator-associated pneumonia, bacteremia, cystitis, and tracheitis. The patient had persistently low absolute counts in B cells (513 cells/µL), T cells (1,538 cells/µL), and natural killer cells (151 cells/µL) as well as low IgG levels (158 mg/dL) concerning for immunodeficiency. Serum levels of IgA (28 mg/dL) and IgM (72 mg/dL) were normal. Streptococcus pneumoniae IgG antibodies demonstrated adequate immunity for 22 of the 23 serotypes. Tetanus and diphtheria toxoid IgG antibodies were protective. Genetic testing revealed a heterozygous, pathogenic variant in the CR2 gene, which is associated with autosomal recessive CVID caused by CD21 deficiency. The patient was started on intravenous immunoglobulin G (IVIG) infusions with subsequent improvement in recurrent infections.
Although our patient had normal IgA, IgM, and polysaccharide and protein vaccine responses, she was found to have a pathogenic gene variant associated with autosomal recessive CVID in the setting of low IgG and responded clinically to treatment with IVIG. It is unclear if the patient will eventually develop the clinical and laboratory findings of CVID, given this autosomal recessive genetic variant. However, this case suggests a role for early genetic testing in patients who present with recurrent infections, as it may help to guide compassionate treatment decisions and further understanding of the patient’s disease process.
