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Introduction and importance SARS-CoV-2 is a novel infection that has affected millions of people around the world. Complications of the infection may affect multiple systems including cardiovascular, neurological, gastrointestinal, urinary, and pulmonary systems. Hypokalemia, which is a life-threatening condition that may lead to arrhythmia and possibly death, has been noticed in more than half of the COVID-19 patients. Further understanding of the disease process and its complications is necessary to guide in preventing the complications from happening in the first place and finding treatment for patients with an already established complications. Case presentation A 34-year old male from Philippines who lives in Saudi Arabia – Riyadh and works as health care provider with no previous history of any medical illness. Presented by himself to the emergency department (ED) with dry cough, shortness of breath, fever, malaise, and fatigability for five days. On examination (RR 25), (T 38.6 °C) and (O2 89% Room air), on auscultation there was a decrease on air entry bilaterally with scattered crepitations, no wheezing or stridor. Covid-19 swab was positive, (Day 1) potassium 2.91 (mmol/L) magnesium (mmol/L) with normal baseline before getting infected. Clinical discussion Patient while in the hospital was on daily potassium oral and IV replacement with IV magnesium replacement. Investigation showed 24Hr urine potassium 47.3 (mmol/L), 24Hr urine magnesium 5.52 (mmol/L), 24Hr urine Creatinine 9.25 (mmol/L), (TTKG) Transtubular Potassium Gradient 18 and (VBG) PH:7.38, Pco2:44 (mmHg) Po2:55 (mmHg) HCO3:25 (mEq/L). Patient has an increased renal potassium loss with normal VBG on separate days and normal Blood pressure that excludes diseases with associated acidemia or alkalemia. Our patient didn't want to go for any invasive diagnostic procedures and favored to wait for spontaneous recovery. Conclusion We followed up the potassium level of our patient for more than 5 months since he was diagnosed with COVID-19 to find out that he is still having hypokalemia, as well as, hypomagnesemia. Long term complications of COVID-19 infection such as hypokalemia and hypomagnesemia need to be observed and followed up closely to avoid life-threatening arrythmias and seizures. The attention of the scientific community to possible long term or permanent complications is needed to help find preventive measures and treatment for patients with complications., Highlights • COVID-19 is a new disease and its complications are not fully understood. • The alteration of the ACE2 receptors and RAS system dysregulation lasted for 5 months. • Presistent electrolytes disturbance after COVID-19 infection is a burden on both patients and their treating physicians.

Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery. (Funded by King Saud University and others.).

Sphingosine-1-phosphate (S1P) lyase is a vitamin B6-dependent enzyme that degrades sphingosine-1-phosphate in the final step of sphingolipid metabolism. In 2017, a new inherited disorder was described caused by mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). This condition is referred to as SPL insufficiency syndrome (SPLIS) or alternatively as nephrotic syndrome type 14 (NPHS14). Patients with SPLIS exhibit lymphopenia, nephrosis, adrenal insufficiency, and/or neurological defects. No targeted therapy for SPLIS has been reported. Vitamin B6 supplementation has therapeutic activity in some genetic diseases involving B6-dependent enzymes, a finding ascribed largely to the vitamin's chaperone function. We investigated whether B6 supplementation might have activity in SPLIS patients. We retrospectively monitored responses of disease biomarkers in patients supplemented with B6 and measured SPL activity and sphingolipids in B6-treated patient-derived fibroblasts. In two patients, disease biomarkers responded to B6 supplementation. S1P abundance and activity levels increased and sphingolipids decreased in response to B6. One responsive patient is homozygous for an SPL R222Q variant present in almost 30% of SPLIS patients. Molecular modeling suggests the variant distorts the dimer interface which could be overcome by cofactor supplementation. We demonstrate the first potential targeted therapy for SPLIS and suggest that 30% of SPLIS patients might respond to cofactor supplementation.

This article was published Open Access in Immunity, Inflammation and Disease (online) available at http://dx.doi.org/10.1002/iid3.153

BACKGROUND: Alternative medicine is defined as medical therapies that are not regarded as orthodox by the medical profession. The teaching of complementary and alternative medicine (CAM) in medical schools is becoming prevalent worldwide. Only a few studies have been done to assess medical students' attitude toward CAM and the need for CAM courses. MATERIALS AND METHODS: An observational, descriptive, cross-sectional study was conducted on medical students in two universities, King Saud (KSU) and Majmaah (MU) medical colleges, between February and April 2015. A survey was developed and validated by a pilot study. Data were gathered from both colleges by means of hard and soft copy surveys. Medical students of both genders from the 1st year to the 5th year from both universities were targeted in this study. Fifth-year students from Majmaah and students from the preparatory year were excluded from the study. KSU students comprised 1433, while MU students comprised only 180. The sample size was 384. Data were analyzed using SPSS software. RESULTS: The study included 399 medical students. Bloodletting is the most known modality (80.7%), while homeopathy is the least known with a percentage of 7.47%. The overall assessment of the attitude toward CAM was neutral, with a mean of 3.1. Students who had taken a CAM course previously were more satisfied with their knowledge than those who had not, showing a statistical significance of P = 0.0001. CONCLUSION: This study showed a lack of knowledge of CAM among medical students. There was an association between taking a CAM course and students' satisfaction with their knowledge. Most of the students agreed with the inclusion of CAM courses in the medical curriculum.

Objective: Major sand storms are frequent in the Middle East. This study aims to investigate the role of air particulate matter (PM) level in acute asthma in children in Riyadh, Saudi Arabia. Methods: An aerosol spectrometer was used to evaluate PM < 10μm in diameter (PM 10 ) and PM < 2.5 μm in diameter (PM 2.5 ) concentrations in the air every 30 minutes throughout February and March 2012 in Riyadh. Data on children 2-12 years of age presenting to the emergency department of a major children′s hospital with acute asthma during the same period were collected including their acute asthma severity score. Results: The median with interquartile range (IQR) levels of PM 10 and PM 2.5 were 454 μg/m 3 (309,864) and 108 μg/m 3 (72,192) respectively. There was no correlation between the average daily PM 10 levels and the average number of children presenting with acute asthma per day (r = -0.14, P = 0.45), their daily asthma score (r = 0.014, P = 0.94), or admission rate ( r= -0.08, P = 0.65). This was also true for average daily PM 2.5 levels. In addition, there was no difference in these variables between days with PM 10 >1000 μg/m 3 , representing major sand storms, plus the following 5 days and other days with PM 10 < 1000 μg/m 3 . Conclusion: Sand storms, even major ones, had no significant impact on acute asthma exacerbations in children in Riyadh, Saudi Arabia. The very high levels of PM, however, deserve further studying especially of their long-term effects.

Objective To investigate the characteristics of patients presenting to the emergency department with anaphylaxis in Saudi Arabia. Methods Records of adults and children who presented to the emergency department of a major tertiary health care center in Riyadh from 2009 to 2012 with a diagnosis of “allergy” or “allergic reaction” were reviewed to identify patients with symptoms and signs fulfilling the criteria of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network for anaphylaxis. Results Out of 1522 records, 62 patients fulfilled the criteria for anaphylaxis. Among them 39 (63%) were adults and 23 (37%) were children (≤12 years of age). Overall, the mean age (±SD) of patients was 21.6 (±16) years. There were 38 (61%) males. Food was the most common trigger, but details of the triggering agents were poorly recorded and 55% of patients could not identify a specific trigger. Asthma was found to be a risk factor for anaphylaxis. There was a marked under prescription of adrenaline auto-injector on discharge. Only few patients were referred to an allergist. Conclusion Our patient population with anaphylaxis had similar characteristics to those in the literature. There is an urgent need to educate emergency department physicians about the guidelines of anaphylaxis management and the importance of gathering specific data.

Background Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, have also been suggested as a therapy for acute asthma when given at high doses. Methods A double-blind, randomized, placebo-controlled trial was conducted in children aged 2 to 12 years with moderate or severe acute asthma, as determined based on a clinical score of 5 to 15 points, where 15 is the most severe. We compared the addition of budesonide 1,500 μg vs placebo to standard acute asthma treatment, which included salbutamol, ipratropium bromide, and a single dose of prednisolone 2 mg/kg given at the beginning of therapy. The primary outcome was hospital admission rate within 4 h. Results A total of 906 ED visits by children with moderate or severe acute asthma were evaluated. Seventy-five cases out of 458 (16.4%) in the budesonide group vs 82 of 448 (18.3%) in the placebo group were admitted (OR, 0.84; 95% CI, 0.58-1.23; P = .38). However, among cases with high baseline clinical score (≥ 13), significantly fewer children were admitted in the budesonide group (27 of 76 [35.5%]) than in the placebo group (39 of 73 [53.4%]; OR, 0.42; 95% CI, 0.19-0.94; P = .03). Conclusions The addition of budesonide nebulization did not decrease the admission rate of children with acute asthma overall. However, it may decrease the admission rate of children with severe acute asthma. Trial registry ClinicalTrials.gov; No.: NCT01524198; URL: www.clinicaltrials.gov

IFN-γhas been used in the treatment of IL-12Rβ1 deficiency patients with disseminated BCG infection (BCGosis), but the optimal dose to reach efficacy is not clear. We used IFN-γin the treatment of a 2.7-year-old patient with IL-12Rβ1 deficiency and refractory BCG-osis. IFNγwas started at a dose of 50 μg/m23 times per week. The dose was upgraded to 100 mcg/m2after 3 months, then to 200 mcg/m26 months afterwards. Serum mycobactericidal activity and lymphocytes number and function were evaluated throughout the study. There was no clinical response to IFN-γwith 50 or 100 μg/m2doses. However, there was some response to the 200 μg/m2dose with no additional adverse effects. The serum mycobactericidal activity was not significantly different during the whole treatment period. Lymphocytes proliferation in response to PHA was significantly higher after 3 months of using the highest dose as compared to the lowest dose. The tuberculin skin test reaction remained persistently negative. We conclude that in a patient with IL-12Rβ1 deficiency, IFN-γat a dose of 200 μg/m2, but not at lower dosages, was found to have a noticeable clinical effect with no additional adverse effects.

True allergic reactions to local anesthetics are extremely rare and constitute less than 1% of all reactions. In addition, many of those allergic reactions are caused by the preservative constituents of the local anesthetics. Here we report a 12year old girl with anaphylaxis to lidocaine (an amide local anesthetic) on two occasions. The allergy was confirmed by positive skin prick test to the drug. Skin testing and challenge to another amide local anesthetic (articaine) were negative. Subsequently, its use was well tolerated in a dental procedure. Up to our knowledge, this is the first report of a patient who is allergic to lidocaine and tolerant to articaine.

International audience; Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous autosomal recessive immune disorder characterized by the occurrence of uncontrolled activation of lymphocytes and macrophages infiltrating multiple organs. Disease-causing mutations in the perforin (PRF1; also known as FHL2), Munc13-4 (UNC13D; also known as FHL3), and syntaxin-11 (STX11; also known as FHL4) genes have been identified in individuals with FHL. These genes all encode proteins involved in the cytotoxic activity of lymphocytes. Here, we show that the gene encoding syntaxin-binding protein 2 (Munc18-2; official gene symbol STXBP2) is mutated in another subset of patients with FHL (designated by us as "FHL5"). Lymphoblasts isolated from these patients had strongly decreased STXBP2 protein expression, and NK cells exhibited impaired cytotoxic granule exocytosis, a defect that could be overcome by ectopic expression of wild-type STXBP2. Furthermore, we provide evidence that syntaxin-11 is the main partner of STXBP2 in lymphocytes, as its expression required the presence of STXBP2. Our work shows that STXBP2 deficiency causes FHL5. These data indicate that STXBP2 is required at a late step of the secretory pathway for the release of cytotoxic granules by binding syntaxin 11, another component of the intracellular membrane fusion machinery.

ObjectiveIn the beginning of 2006 there were major changes to the structure of the pediatrics course that coincided with a sharp increase in the students’ number. We aimed to get the students and teachers evaluation of the different activities of the pediatrics course.MethodsStudents were asked, at the end of each cycle in 4 consecutive cycles from January 2006 to March 2007, to evaluate various course activities based on what they thought was more useful or effective through filling out a short questionnaire. Teachers filled out a similar questionnaire based on what they thought were more useful to the students.ResultsIn 4 consecutive courses 247 (65%) students filled the questionnaire. Overall, the students favored tutorial and small group case discussion sessions over lectures (P

Dysmorphology syndromes are among the most common referrals to clinical genetics specialists. Inability to match the dysmorphology pattern to a known syndrome can pose a major diagnostic challenge. With an aim to accelerate the establishment of new syndromes and their genetic etiology, we describe our experience with multiplex consanguineous families that appeared to represent novel autosomal recessive dysmorphology syndromes at the time of evaluation. Combined autozygome/exome analysis of multiplex consanguineous families with apparently novel dysmorphology syndromes. Consistent with the apparent novelty of the phenotypes, our analysis revealed a strong candidate variant in genes that were novel at the time of the analysis in the majority of cases, and 10 of these genes are published here for the first time as novel candidates (CDK9, NEK9, ZNF668, TTC28, MBL2, CADPS, CACNA1H, HYAL2, CTU2, and C3ORF17). A significant minority of the phenotypes (6/31, 19%), however, were caused by genes known to cause Mendelian phenotypes, thus expanding the phenotypic spectrum of the diseases linked to these genes. The conspicuous inheritance pattern and the highly specific phenotypes appear to have contributed to the high yield (90%) of plausible molecular diagnoses in our study cohort. Reporting detailed clinical and genomic analysis of a large series of apparently novel dysmorphology syndromes will likely lead to a trend to accelerate the establishment of novel syndromes and their underlying genes through open exchange of data for the benefit of patients, their families, health-care providers, and the research community. Genet Med 18 7, 686–695.

Background\ud \ud Current evidence suggests that inhaled glucocorticoids (IGC) have a more profound topical none genomic effect on bronchial airways as compared to systemic glucocorticoids. The value of adding IGC to current therapy of acute asthma is not well established.\ud Methods\ud \ud We conducted a double-blind, randomized, two-arm, parallel groups, controlled clinical trial to compare the addition of budesonide 1500 mcg or placebo (normal saline) to standard acute asthma treatment (albuterol and ipratropium bromide) administered in 3 divided mixed doses within 1 hour in the emergency department (ED). Children 2-12 years of age with moderate or severe acute asthma, scoring 8-15/15 on a well-validated scoring system were included. Both groups received a single dose of prednisone 2 mg/kg/day (max. 60 mg) at the beginning of therapy. The primary outcome was admission rate within 2-4 hours from starting therapy.\ud Results\ud \ud A total of 723 children were enrolled in the study over 17 months duration, of whom 139 were allowed to re-enroll and be randomized to constitute 906 randomization assignments (458 on the treatment group and 448 on the control group); with baseline mean + SD asthma score of 10.63 + 1.73; age 5.52 + 2.76 years; 35% girls; 30.8% (16.5%) with baseline severe asthma score of ≥12 (≥ 13). Statistical Analysis plan allowed for the potential dependency in response due to reenrollments of a subset of children, using Generalized Linear Mixed Modeling (GLMM) techniques. Baseline demographic and clinical characteristics were not significantly different between the two randomized groups. Seventy-five out of 458 (16.4%) of the treatment group vs. 82/448 (18.3%) of the control group were admitted, (OR 0.85, CI: 0.59-1.23, p-value=0.39). Among the severe asthmatics with baseline score ≥13, treatment vs. placebo group, GLMM adjusted admission rate was 30% vs. 47%, indicating a 17% difference in admission rate in favor of the treatment group (adjusted OR of 0.49, CI: 0.25-0.95; p-value= 0.035) that indicated a 51% reduction in the risk of admission for the treatment vs. control group.\ud Conclusions\ud \ud Children with baseline severe asthma score ≥13 who were treated with budesonide had a significant reduction in their admission rate.

BACKGROUND AND OBJECTIVES: Genetic association studies have demonstrated that over 100 variants in target genes (including ADAM33) are associated with airway remodeling and hyper-responsiveness in different ethnic groups; however, this has never been evaluated in Arabic populations. The objective of this study was to determine whether ADAM33 polymorphisms that are associated with asthma in a population of asthmatic children from Saudi Arabia. DESIGN AND SETTING: A cross-sectional pilot study comparing the polymorphisms of normal subjects and asthmatic patients from Saudi Arabia over a period of 1 year. PATIENTS AND METHODS: One hundred and seven Saudi asthmatic children and 87 healthy Saudi children of 3–12 years old were assessed for allelic association of ADAM33 T1 (rs2280091), T2 (rs2280090), ST+4 (rs44707) and S1 (rs3918396) SNPs to asthma. Genotyping was done by real-time PCR, multiplex ARMS and PCR-RFLP. RESULTS: T1 and T2 SNP genotype frequencies in asthmatic children were significantly different compared to controls (P

Herpes simplex encephalitis (HSE) is the most common sporadic viral encephalitis of childhood. Autosomal recessive (AR) UNC-93B and TLR3 deficiencies and autosomal dominant (AD) TLR3 and TRAF3 deficiencies underlie HSE in some children. We report here unrelated HSE children with AR or AD TRIF deficiency. The AR form of the disease was found to be due to a homozygous nonsense mutation that resulted in a complete absence of the TRIF protein. Both the TLR3- and the TRIF-dependent TLR4 signaling pathways were abolished. The AD form of disease was found to be due to a heterozygous missense mutation, resulting in a dysfunctional protein. In this form of the disease, the TLR3 signaling pathway was impaired, whereas the TRIF-dependent TLR4 pathway was unaffected. Both patients, however, showed reduced capacity to respond to stimulation of the DExD/H-box helicases pathway. To date, the TRIF-deficient patients with HSE described herein have suffered from no other infections. Moreover, as observed in patients with other genetic etiologies of HSE, clinical penetrance was found to be incomplete, as some HSV-1–infected TRIF-deficient relatives have not developed HSE. Our results provide what we believe to be the first description of human TRIF deficiency and a new genetic etiology for HSE. They suggest that the TRIF-dependent TLR4 and DExD/H-box helicase pathways are largely redundant in host defense. They further demonstrate the importance of TRIF for the TLR3-dependent production of antiviral IFNs in the CNS during primary infection with HSV-1 in childhood.

WOS: 000283840300002, PubMed ID: 21057261, Interleukin-12 receptor beta 1 (IL-12R beta 1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guerin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years +/- 9.8 years (range, 0.5-46.4 yr). IL-12R beta 1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought., Rockefeller University Center for Clinical and Translational Science [5UL1RR024143-03]; Rockefeller University; ANRFrench National Research Agency (ANR); PHRC; EUEuropean Union (EU) [LHSP-CT-2005-018736]; BNP Paribas Foundation; Dana Foundation; March of DimesMarch of Dimes; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale; Howard Hughes Medical InstituteHoward Hughes Medical Institute, The St. Giles Laboratory of Human Genetics of Infectious Diseases is supported by grants from The Rockefeller University Center for Clinical and Translational Science grant number 5UL1RR024143-03, and The Rockefeller University, ANR, PHRC, EU (LHSP-CT-2005-018736), BNP Paribas Foundation, the Dana Foundation, and the March of Dimes. LDB is supported by the Fondation pour la Recherche Medicale as part of the PhD program of Pierre et Marie Curie University (Paris, France). JLC was an International Scholar of the Howard Hughes Medical Institute.

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients with an Arabic ethnic background. We report on two Saudi girls with PNP deficiency. Both showed severe lymphopenia and neurological involvement. Sequencing of the PNP gene of one girl revealed a novel missense mutation Pro146>Leu in exon 4 due to a change in the codon from CCT>CTT. Expression of PNP (146L) cDNA in E coli indicated that the mutation greatly reduced, but did not completely eliminate PNP activity.

To evaluate the effect of intravenous immunoglobulin IVIG utilization at King Khalid University Hospital, an 850 bed tertiary care academic center, over a-3-year period.Patients who received IVIG in the period from January 2003 to December 2005 at King Khalid University Hospital were identified retrospectively using the hospital computer system. Their charts were subsequently reviewed. We collected data pertaining to patients' demographics, indication of IVIG, dose regimen and physician specialty. Indications were categorized into 4 different categories: US Food and Drug Administration FDA-labeled; off-label recommended as first line; off-label recommended as alternative; and not recommended.A total of 305 patients were identified. Intravenous immunoglobulin was given to 109 (35.7%) patients for FDA-labeled indications, 29 (9.5%) patients for off-label recommended as first line indications, 97 (31.8%) for off-label recommended as alternative indications, and 70 (23%) for not recommended indications. The amount of IVIG consumed during the study period was 43.65 Kgs with an estimated cost of $1.75 million, 24.4% of which was considered inappropriate use. Hematologists and neurologists were the most frequent prescribers.A significant amount of IVIG was prescribed for inappropriate indications. This had a large financial burden on an already strained hospital budget.

Background A number of heritable immune dysregulatory diseases result from defects affecting regulatory T (Treg) cell development, function, or both. They include immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, which is caused by mutations in forkhead box P3 (FOXP3) , and IPEX-like disorders caused by mutations in IL-2 receptor α (IL2RA) , signal transducer and activator of transcription 5b (STAT5b) , and signal transducer and activator of transcription 1 (STAT1) . However, the genetic defects underlying many cases of IPEX-like disorders remain unknown. Objective We sought to identify the genetic abnormalities in patients with idiopathic IPEX-like disorders. Methods We performed whole-exome and targeted gene sequencing and phenotypic and functional analyses of Treg cells. Results A child who presented with an IPEX-like syndrome and severe Treg cell deficiency was found to harbor a nonsense mutation in the gene encoding LPS-responsive beige-like anchor (LRBA), which was previously implicated as a cause of common variable immunodeficiency with autoimmunity. Analysis of subjects with LRBA deficiency revealed marked Treg cell depletion; profoundly decreased expression of canonical Treg cell markers, including FOXP3, CD25, Helios, and cytotoxic T lymphocyte–associated antigen 4; and impaired Treg cell–mediated suppression. There was skewing in favor of memory T cells and intense autoantibody production, with marked expansion of T follicular helper and contraction of T follicular regulatory cells. Whereas the frequency of recent thymic emigrants and the differentiation of induced Treg cells were normal, LRBA-deficient T cells exhibited increased apoptosis and reduced activities of the metabolic sensors mammalian target of rapamycin complexes 1 and 2. Conclusion LRBA deficiency is a novel cause of IPEX-like syndrome and Treg cell deficiency associated with metabolic dysfunction and increased apoptosis of Treg cells.

Background Clinical immunology has traditionally relied on accurate phenotyping of the patient's immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis. Objective We sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease–like disorder and combined immunodeficiency. Methods We performed exome sequencing followed by autozygome filtration. Results A truncating mutation in LPS-responsive beige-like anchor ( LRBA ), which abolished protein expression, was identified as the most likely candidate variant in this family. Conclusion The combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.

Glucocorticoids are the mainstay of asthma therapy. They are primarily used to suppress airway inflammation, which is the central pathological change in asthmatic patients' airways. This is achieved by many different mechanisms. The classical mechanism is by suppression of the genetic transcription of many inflammatory cytokines that are key in asthma pathophysiology (transrepression). On the other hand, the transcription of certain inhibitory cytokines is activated by glucocorticoids (transactivation), a mechanism that also mediates many of the adverse effects of glucocorticoids. The onset of action through these mechanisms is often delayed (4-24 hours). Other mechanisms mediated through non-genomic pathways are increasingly appreciated. These are delivered in part by binding of glucocorticoids to nonclassical membrane-bound glucocorticoid receptors or by potentiating the α1-adrenergic action on the bronchial arterial smooth muscles, in addition to other mechanisms. These effects are characterized by their rapid onset and short duration of action. Understanding these different mechanisms will help in the development of new and better drugs to treat this common disease and to develop new improved strategies in our approach to its management. Here, the genomic and non-genomic mechanisms of actions of glucocorticoids in asthma are briefly reviewed, with special emphasis on the current updates of the non-genomic mechanisms.

[This corrects the article DOI: 10.1016/j.idcr.2019.e00565.]., (© 2019 Elsevier Ltd. All rights reserved.)