Hereditary angioedema (HAE) is a potentially life-threatening autosomal dominant disorder affecting roughly 1:50,000 individuals. It is commonly characterized by swelling of the larynx, gastrointestinal tract, extremities, and skin. There is growing genetic heterogeneity associated with this disease but more than 95% of mutations are found in SERPING1, the gene which encodes complement 1 inhibitor (C1-INH). HAE cohorts from several populations have been published but no large scale study has been reported from the Arab world to date. Here we document the clinical and genetic findings of HAE patients from a single Saudi institution, which is a major referral center at the national level. A total of 51 patients across 17 unrelated families were recruited including two large multi-generational families, of which one contained an in-frame exonic deletion that was resolved through MLPA. Two cases were negative for all the genes we tested (including F12, PLG, ANGPT1, MYOF, KNG1, and HS3ST6). The predominant HAE subtype in our cohort was type I, at 76%. We were able to uncover a mutation in 49 patients (96%). No type III (normal C1-INH) patients were encountered in the clinic, suggesting that this subtype does not play a major role in HAE pathogenesis in Saudi Arabia. Additionally, the existence of four patients with consistently normal complement 4 (C4) levels alongside abnormal C1-INH profiles highlights the utility of dual screening for both proteins in suspected patients.

Background: Primary immune deficiency (PID) patients may develop acute or chronic pain. Pain has not been studied in this population until now. Objectives: This study systematically assessed the pain of various durations in PID patients using validated pain questionnaires. Subjects and Methods: A Short-Form McGill Pain Questionnaire (SF-MPQ), already validated in the Arabic language, was used to ascertain the characteristics and severity of pain. Additionally, an Arabic version of the Neuropathic Pain Questionnaire-Short Form (NPQ-SF) was employed to evaluate neuropathic pain in the same group of patients. Results: Forty-six patients participated in the study. The mean age of the patients was 25 years. The most commonly diagnosed PID was a common variable immune deficiency (32.6%), followed by severe combined immune deficiency (19.57%). Based on the SF-MPQ, the pain was experienced by 30.4 % of the subjects who participated in the study; 57% of whom were on regular pain medications. The most common site reported for pain was the abdomen (35.7%). The mean duration of pain was 36.1 days ± 34.6 days. The most common comorbidities in these patients were bronchiectasis, followed by immune thrombocytopenic purpura, and scoliosis. None of the PID patients had significant neuropathic pain based on NFQ-SF. Conclusion: To the best of our knowledge, this is the first study to assess the prevalence as well as the severity and duration of pain in PID patients. There were significantly more subjects who had continuous pain. Treatment of pain in PID patients will have a significant effect on improving their quality of life.

Hyper-IgM syndrome (HIGM) due to CD40 deficiency is a very rare form of combined immunodeficiency with increased susceptibility to opportunistic infections. Cryptococcus is an opportunistic infection usually affecting immunocompromised individuals. This is the first report to describe a patient with HIGM due to CD40 deficiency presenting with meningoencephalitis secondary to Cryptococcus infection.