Recurrent Infections in a 5-Year-Old Boy

Nicholas Bennett, MBBChir, PhD


July 30, 2018

Transient hypogammaglobulinemia of infancy (THI) is a form of hypogammaglobulinemia that appears shortly after birth, with decreased levels of IgG and sometimes decreased levels of IgA and IgM. Symptoms are similar to those of CVID in regard to recurrent bacterial infections but present earlier in life (ages 6 to 12 months), and the condition typically resolves without treatment within a year's time. THI is a diagnosis of exclusion that occurs in the absence of other primary immunodeficiencies.

X-linked hypogammaglobulinemia, Bruton agammaglobulinemia, or X-linked agammaglobulinemia (XLA) is a rare genetic disorder inherited in an X-linked recessive fashion. XLA primarily affects males due to an X-linked mutation at the Bruton tyrosine kinase (Btk) gene, which blocks B-cell development and markedly reduces immunoglobulin production. Boys typically present in early childhood with recurrent, potentially fatal, infections due to extracellular, encapsulated bacteria. Given the serological detection of IgG in the patient in this case, this diagnosis is unlikely.

22q11.2 deletion syndrome, also known as DiGeorge syndrome or velocardiofacial syndrome, is due to a deletion of genetic material on chromosome 22. This microdeletion syndrome leads to a defect in the embryonic development of the third and fourth branchial arches, which can lead to thymic dysplasia and subsequent defects in B-cell immunity due to a lack of helper T-cell activity. Craniofacial findings can include narrow palpebral fissures, cupped ears with narrow tortuous ear canals, broad nasal bridge, wide mouth with a thin upper lip, cleft lip and palate, and weakened dental enamel. Speech may be hypernasal. Patients may have history of congenital heart disease and low serum calcium (hypocalcemia). Developmental delays and learning disabilities are often present. Ear infections are common in early childhood but are more likely due to anatomic defects than humoral immune defects. Lower respiratory infections are uncommon. Although DiGeorge syndrome has a higher prevalence worldwide (around 1 case per 4000 population vs 1 in 25000 for CVID), given the absence of phenotypic findings and the medical history of the patient in this case, the diagnosis of 22q11.2 deletion syndrome is unlikely.

Recent analysis of immune function in children with recurrent otitis media have revealed low vaccine titers and antigen-specific memory B-cell responses; however, these observations may reflect a continuum of immune function, from normality to true disease.[3,4,5,6] Etiology for a high rate of vaccine failure is unclear. One theory is that because many of these children are diagnosed with asthma and atopy they are frequently prescribed systemic steroids for treatment, which leads to blunted vaccine responses. Their immune system may also be skewed toward an atopic cytokine milieu, hampering normal B-cell function. The vast majority of these children respond appropriately to booster immunizations with pneumococcal vaccine, with no demonstrable loss of immune memory.


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