Transient hypogammaglobulinemia infancy

Diagnosis

While THI may be suspected in an infant, the diagnosis can only be made once IgG levels have normalized, showing that the low level was temporary and not the result of another type of immunodeficiency. In other words, THI can only be officially diagnosed looking back over time.

The criteria for diagnosing THI include an IgG level that is lower than 95% of children of similar age (at least two standard deviations below the average level) when measured on at least two separate occasions. Other immunoglobulins, including IgA and IgM, might be normal or low in infants with THI.

Other immunodeficiencies must be ruled out prior to making the diagnosis. When the IgG is very low, or when all immunoglobulins are low, an alternate diagnosis should be considered. There are no specific findings on physical examination that help make the diagnosis of THI.

The evaluation should include checking antibody levels (titers) to things against which the child has been previously vaccinated, such as tetanus and pneumococcal vaccines. Most children with THI are able to make antibodies to vaccines. However, if vaccine titers are low, a booster dose of the vaccine may be given and antibody levels measured again after 4-6 weeks to evaluate the immune response. Immune memory may be evaluated by rechecking the vaccine antibody levels again in six months. If a child does not make antibodies to vaccines, consultation with an immunologist is indicated.

A complete blood count (CBC) with differential to check the numbers of white blood cells, especially the lymphocytes, is important in the work-up of THI. If lymphopenia, a low number or percent of lymphocytes, is present along with low IgG levels, additional studies will be necessary and consultation with an immunologist is warranted. This is because low lymphocyte numbers are not typically seen in THI and may be a sign of another type of PI. Additional reasons for consultation with an immunologist are severe or persistent infections, unusual infections, poor growth, chronic diarrhea, or IgG levels that do not improve over time.

It is important to rule out other causes of low IgG during the evaluation, including B cell defects (such as X-linked agammaglobulinemia) and combined T and B cell defects (such as severe combined immunodeficiency). In addition, it is important to rule out loss of IgG as a possible cause of a low IgG level. In THI, the IgG is low because the infant has trouble making IgG, which is a production problem. In contrast, some infants make normal levels of IgG but quickly lose it, such as infants with various gastrointestinal, heart, or kidney diseases.

Expectations

Children who have low IgG levels should be closely followed, because low IgG can increase the risk for infections. Monitoring includes checking immunoglobulin and specific antibody levels, tracking growth, and evaluating for other possible causes of low IgG. The expectation is that IgG levels will normalize between 2-5 years of age.

If monitoring reveals persistently low immunoglobulin levels and/or low responses to vaccines, a different diagnosis should be considered. Some children initially suspected to have THI are later diagnosed with another antibody disorder such as common variable immune deficiency (CVID) or specific antibody deficiency when their THI does not resolve. Careful monitoring is important for this reason.

Until it is demonstrated that the child has normal production of antibodies, live viral vaccines, such as rotavirus, MMR, and chickenpox, should not be given. If a child has an impaired response to these vaccines, it is possible to contract the illness after vaccination.