Diagnostic evaluation of AICs in pediatric and adult patients. A systematic, interdisciplinary approach can facilitate a timely and accurate diagnosis in these patients. All patients should receive a basic evaluation (expanded in Table 1), followed by immunological assessment (immunophenotyping, functional, and other specific assays), based on clinical phenotype, family history, and age of onset of symptoms. Molecular/genetic testing can be pursued either in parallel to the immunological assessment, depending on the clinical phenotype, or sequential to it. If a molecular diagnosis is not established at the first attempt, and if the likelihood of a genetic defect is high, recommend an iterative approach, which can also be used when characterizing VUSs. In the older adult, secondary causes of AIC should be eliminated before considering an intrinsic immune anomaly as the cause of the phenotype. This figure was created with BioRender.com.