Phenotypic and Genotypic Characterization of Hereditary Angioedema in Saudi Arabia.

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.

A COVID-19 family cluster with retinitis pigmentosa and hypogammaglobulinemia.

Hypogammaglobulinemia is a heterogeneous group of innate and acquired antibody deficiency with variable disease severity, recurrent pneumonia, and bronchiectasis. The outcome of COVID in patients with hypogammaglobulinemia is variable depending on age, comorbidities, type of immunodeficiency, and use of immunoglobulins. We report the favorable outcome of two family members diagnosed with DNAJC17-related retinitis pigmentosa and hypogammaglobulinemia syndrome and infected with SARS-CoV-2 following contact with their mother who had COVID-19. We describe the different immune dysfunction in these patients and their impact on the course and management of SARS-CoV-2 infection.

Novel influenza A (H1N1) virus-induced hemophagocytosis: first case reported in Saudi Arabia.

H1N1 is a novel subtype of the influenza A virus. Since its reemergence in 2008, it has been reported to cause a variety of illnesses ranging from mild flu-like symptoms to severe multiorgan failure. We report a case of a young immunocompetent man who presented with progressive shortness of breath and rapidly developed multiorgan dysfunction, including pancytopenia from H1N1 infection during the 2010-2011 influenza season. His H1N1 pneumonia caused severe acute respiratory distress syndrome, respiratory failure requiring mechanical ventilation, rhabdomyolysis, myocarditis, hepatitis, encephalitis, and renal failure. During the diagnostic workup, a bone marrow biopsy was performed, showing hemophagocytosis secondary to the H1N1 infection. Unfortunately the patient died despite aggressive measures. Published reports contain only a few records of H1N1-induced hemophagocytosis. This is the first case report from Saudi Arabia with H1N1-induced secondary hemophagocytosis. It also highlights the fact that the virus is still very virulent and will pose a major annual health risk along with the seasonal influenza for at least the next few years.