Lipopolysaccharide Responsive Beige-like Anchor Protein Deficiency in a Patient with Autoimmune Lymphoproliferative Syndrome-like Disease Phenotype: A Case Report and Literature Review.

LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency caused by a mutation in the LRBA gene. Affected individuals present with a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, splenomegaly, hepatomegaly, and autoimmune cytopenias. Except for hypogammaglobulinemia, the remaining features resemble autoimmune lymphoproliferative syndrome (ALPS). Here, we report the case of a 14-year-old boy with the ALPS phenotype, eventually diagnosed with LRBA deficiency. He presented with lymphadenopathy and hepatosplenomegaly, along with autoimmune cytopenia. Due to recurrent infections and worsening gastrointestinal symptoms, whole-exome sequencing was conducted and revealed a novel homozygous pathogenic variant in the LRBA gene (c.534del; p.9Asp179IIef*16). The patient recently suffered from clinical deterioration due to SARS-COV-2 which appears to have triggered an acute worsening of his existing Cytomegalovirus colitis leading to an eventual demise. A literature search for reported LRBA deficient patients with ALPS-like phenotype revealed 11 patients. The most common clinical presentations in LRBA patients with ALPS-like phenotype included autoimmunity (100%), splenomegaly (91%), lymphadenopathy (36.4%), and respiratory tract infections (63.6%). LRBA deficiency is unique in the fact that it encompasses immune deficiency, autoimmunity, and lymphoproliferation. In children with multiple symptoms related to these domains, a genetic diagnosis is necessary to ensure tailored and precise medical therapy.

Assessing and addressing barriers towards MDI use in acute asthma exacerbations at a tertiary pediatric ED in the United Arab Emirates.

Asthma is one of the most common causes of emergency department (ED) visits in children. Therapy delivered through a meter dose inhaler with spacer (MDI + S) is equally as effective as nebulization in mild and moderate asthma exacerbations but was not routinely prescribed in the ED at the largest tertiary center for pediatrics in the United Arab Emirates (UAE). Phase 1 of this cohort study involved a validated survey to evaluate physicians' knowledge, attitudes and perceptions towards MDI therapy. While 62% of physicians reported that MDI + S was equally effective as nebulizers and 82% believed that they had sufficient knowledge with regard to its use, only 28% prescribed it. Perceived barriers to change of practice included: Lack of clinical practice guidelines (CPG), poor knowledge amongst nurses and physicians, caregivers' reluctance and a difficult prescription process. Phase 2 consisted of administering the same survey after completing interventions to address the aforementioned barriers. Comparisons were made between the subgroups within phase 1 and statistically significant differences were noted with a p value < .05. The number of physicians who prescribed MDI + S increased from 28% to 41% (p value = .046). Moreover, physicians who believed that convincing parents to use MDI + S therapy would be easy, increased from 35% to 66% (p value < .0001). In conclusion, more physicians reported prescribing MDI + S in Phase 2 while concerns about barriers that exist to change in practice remained similar in both phases showing that consistent and prolonged advocacy is required to achieve long-term compliance.

Novel mutation causing propionic acidemia associated with unexplained autoimmune thyrotoxicosis.

Propionic acidemia (PA) is a rare autosomal recessive inborn error of metabolism (IEM) with relatively higher prevalence in the United Arab Emirates (UAE). Absence of propionyl-CoA carboxylase (PCC) enzyme classically leads to acute decompensation in the early neonatal period. We report a novel homozygous frameshift variant c.2158_2159insT; p.Glu720Valfs*14 (NM_000282.3) in the last exon of the PCCA gene which led to a severe presentation of PA in a newborn Emirati female. Uniquely the diagnosis remained unclear since newborn screening revealed an isolated elevation in plasma proprionylcarnitine (C3) while urinary organic acids remained persistently negative for the classic biochemical abnormalities even during the period of critical illness. Additionally, the patient had an unexplained diagnosis of neonatal thyrotoxicosis. This case explores possible underlying causes through an extensive literature search. To date, there have been no similar reported cases in existing literature.