Based on the International Consensus Document (ICON) guidelines, it is defined by four main criteria: (1) a low IgG level (below the age-appropriate range on two tests at least 3 weeks apart, unless very low—typically <100–300 mg/dL depending on age), (2) low IgA and/or IgM levels, (3) poor antibody responses to vaccination, and (4) the exclusion of other causes of hypogammaglobulinemia [1]. Here, CD40LG is linked to agammaglobulinemia.