Unmasked by Pregnancy: A Case of Latent Hypogammaglobulinemia with a Familial Link to CVID

IntroductionHypogammaglobinemia in pregnancy can be an expected physiological change, resulting from hemodilution and active transfer of immunoglobulins to the fetus via the placenta. However, pregnancy can also reveal pathological causes of hypogammaglobinemia. Here, we present a case of a mother with normal prepregnancy IgG levels, whose predisposition for hypogammaglobulinemia was revealed only during pregnancy. This underlying genetic susceptibility for hypogammaglobulinemia is further suggested by her son’s diagnosis of common variable immunodeficiency (CVID) requiring immunoglobulin replacement therapy (IgRT).Case DescriptionA 30-year-old (G3P2) female, at 21 weeks of gestation, presents with low immunoglobulin levels. She was symptomatic during her pregnancy with recurrent sinusitis, Streptococcus pharyngitis, and several viral infections. Her IgG levels had decreased from a prepregnancy baseline of 849 mg/dL to 567 mg/dL. Her IgA and IgM similarly decreased from 58 and 146 mg/dL to 45 and 137 mg/dL, respectfully. She also showed evidence of specific antibody deficiency with poor durability of titers against tetanus, rubella, and pneumococcus, despite having been fully immunized to all of these microbes during childhood.Her family history is significant for CVID in her son and a maternal cousin who passed away from an undefined immunodeficiency disorder. Her son’s inborn error of immunity (IEI) genetic panel failed to identify the gene responsible for his CVID.The patient was started on subcutaneous IgRT for the remainder of the pregnancy, which improved her IgG levels to 580–657 mg/dL. Three months post-partum, after discontinuing IgRT, her IgG level rebounded to 696 mg/dL, and ultimately to her prepregnancy IgG level. To prevent infectious complications in her subsequent pregnancies, she was preemptively started on IgRT at the end of the second trimester during each pregnancy.DiscussionThis case highlights a predisposition to hypogammaglobulinemia that was unmasked by the physiological stress of pregnancy in an otherwise asymptomatic woman. This patient’s course suggests a transient, stress-induced manifestation of a yet-to-be-defined genetic condition. We hypothesize that the genetic defect in this family may be X-linked, as evidenced by a more severe humoral defect in her male offspring.