**4.4 Immunodeficiency syndromes**

PID patients may also present with a syndrome complex. For example, recurrent bacterial/fungal infections and chronic inflammation of the gastrointestinal and respiratory tract often present in patients with chronic granulomatous disease, while an individual suffering from Wiskott-Aldrich syndrome may have manifestations of eczema, recurrent bacterial infections, autoimmune disorders, and thrombocytopenia [27]. In addition, congenital heart disease and hypocalcemic tetany frequently appear in a newborn baby with the DiGeorge syndrome [28, 29]. In fact, the investigation of patients with a syndrome derived from immunodeficiency may trigger an early diagnosis of PID before the typical immunodeficiency symptoms appear [4].

### **4.5 Malignancy**

Compared to individuals with a healthy immune system, patients with PID are expected to have higher prevalence and/or broader spectrum of malignancies [30]. A study showed that lymphoma, the most common malignancy seen in PID patients, has increased 10-folds in male and 8.34-folds in female compared to age-matched controls [31]. Other types of cancer with higher frequency in PIDs are leukemia, digestive tract cancers, and virus-induced cancers [30]. Interestingly, the four most common cancers routinely occurred in men and women (lung, colon, breast, and prostate cancers) do not have significant elevation in subjects diagnosed with PID [31]. Evidence also demonstrated that patients with specific forms of immunodeficiency caused by highly penetrant gene defects have higher risk of developing cancer [32].
