Chronic granulomatous disease in the United Arab Emirates: clinical and molecular characteristics in a single center.

Background: Chronic granulomatous disease (CGD) is a genetic disorder caused by defective oxidative burst within phagocytes, manifesting as recurrent, severe infections as well as hyperinflammation. Objective: This is the first report from the United Arab Emirates (UAE) to describe the demographic, clinical, laboratory, radiological, and genetic characteristics of patients with CGD. Methods: This is a retrospective study that was conducted at Tawam Hospital in the UAE on patients with confirmed CGD between 2017 and 2022. Results: A total of 14 patients were diagnosed with CGD, of whom 13 patients had autosomal recessive (AR) CGD due to NCF1 deficiency. Consanguinity was noted in all patients with AR CGD, whereas positive family history was identified in 50% of cases. The median age of onset of symptoms was 24 months, while the median age at diagnosis was 72 months. Lymphadenitis was the most common clinical feature identified in 71% of patients. Other common infectious manifestations included abscess formation (57%), pneumonia (50%), invasive aspergillosis (21%), oral thrush (14%), and sepsis (14%). Disseminated trichosporonosis was reported in one patient. Autoimmune and inflammatory manifestations included celiac disease in two patients, diabetes mellitus and asymptomatic colitis in one patient each. Genetic analysis was performed in all patients; NCF1 deficiency was diagnosed in 13 (93%) patients, with c.579G>A being the most prevalent pathogenic variant identified. The treatment modalities, as well as treatment of acute infections, treatment modalities included antimicrobial prophylaxis in 12 (86%) patients and hematopoietic stem cell transplant in six patients (42%). Conclusion: This is the first report from the UAE describing the clinical and molecular characteristics of patients with CGD. The homozygous variant c.579G>A causing NCF1 deficiency can be considered as a founder mutation for AR CGD in the UAE.

Clinical Outcomes of COVID-19 in Newborns and Infants: A Multicenter Experience of 576 Cases.

BACKGROUND: The literature describing clinical presentation, disease course and outcomes of SARS-CoV-2 in infants remains scarce. METHODS: We conducted a retrospective study across 2 major pediatric referral centers evaluating the demographics, clinical and laboratory characteristics, management and outcomes of COVID-19 among newborns and infants in the United Arab Emirates (UAE). Clinical and biochemical markers were evaluated for their accuracy in predicting intensive care unit (ICU) transfer and death. RESULTS: A total of 576 COVID-19-positive infants were evaluated with a mean age of 164 days. The mean duration of symptoms was 1.48 days. Fever was present in 36.5% of the cohort, while 44.3% had nasal congestion. Eight infants (of 575; 1.39%) required transfer to the ICU for impending respiratory failure and 2 required invasive ventilation. Symptomatic (fever, nasal congestion) infants were not more likely to be transferred to the ICU (Chi-squared test, P = 0.77). ICU transfer was associated with a higher chance of receiving antibiotics (70.6% vs 35.4%; Chi-squared test, P = 0.003). On multivariate analysis, none of the clinical parameters (age, symptoms, laboratory tests) predicted transfer to the ICU. No deaths were reported during the observation period. CONCLUSIONS: Infants with SARS-CoV-2 infection have a benign clinical course with favorable outcomes. Less than 2% require ICU transfer. Clinical vigilance is required as none of the admission parameters predicted ICU transfer.

Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency.

Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Herpesviridae viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.

Clinical course of COVID-19 among immunocompromised children: a clinical case series.

Infection with SARS-CoV-2 represents a great source of concern and a new threat for immunocompromised patients. Limited studies are available on COVID-19 in immunocompromised children. This case series aimed to evaluate the clinical and laboratory characteristics, management and outcomes of COVID-19 in five children immunocompromised due to different underlying conditions. All had mild symptoms or were asymptomatic at presentation. All had a benign course of illness. No changes or delays in their treatment regimens occurred, and none experienced a relapse of the original disease, developed severe COVID-19 or died. However, these cases showed a prolonged duration of virus shedding. This report suggests that immunocompromised paediatric patients may not be at a higher risk of developing severe COVID-19. However, further studies are required to elaborate on the pathogenesis of COVID-19 in this vulnerable group.

HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease.

Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in NCKAP1L, which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Thus, the evolutionarily conserved HEM1 protein simultaneously regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune responses.