Epidemiology of combined immunodeficiencies affecting cellular and humoral immunity- a multicentric retrospective cohort study from the Arabian Peninsula.

Aims: To understand the characteristics of combined immunodeficiency disorders that affect cellular and humoral immunity (CID) in the Arabian Peninsula.

Methods: Retrospective study of 236 patients with CID from the region were enrolled from 2004 to 2022.

Results: 236 patients were included with a majority being profound CID.

Predictors of early death risk among untransplanted patients with combined immunodeficiencies affecting cellular and humoral immunity: A multicenter report.

Background: There is an increased demand for hematopoietic stem cell transplant (HSCT) to treat various diseases including combined immunodeficiencies (CID), with limited worldwide availability. Variables affecting the decision regarding CID patients' prioritization for HSCT are not known. We aimed to determine general, clinical, and immunologic factors associated with the higher risk of early death (≤6 months after diagnosis) in untransplanted CID patients.

The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders.

Hermansky-Pudlak Syndrome: Spectrum in Oman.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder, characterized by oculocutaneous albinism, a hemorrhagic diathesis secondary to storage pool-deficient platelets, and in some patients' pulmonary fibrosis, granulomatous colitis, and immunodeficiency. To date, 11 different types of Hermansky-Pudlak syndrome were identified. HPS type 2 is distinctively characterized by severe neutropenia and recurrent sinopulmonary infections.

BCG Vaccine-associated Complications in a Large Cohort of Children With Combined Immunodeficiencies Affecting Cellular and Humoral Immunity.

Aims: To present the details of Bacillus Calmette-Guérin (BCG)-vaccine associated complications (VACs) in combined immunodeficiencies (CID) patients.

Methods: Five centers participated in this retrospective study and completed a data form, which included general patients' information, clinical and laboratory data.

Results: Among 236 CID patients, 127 were BCG vaccinated.

Immune dysregulation caused by homozygous mutations in CBLB.

CBL-B is an E3 ubiquitin ligase that ubiquitinates proteins downstream of immune receptors to downregulate positive signaling cascades. Distinct homozygous mutations in CBLB were identified in 3 unrelated children with early-onset autoimmunity, one of whom also had chronic urticaria. Patient T cells exhibited hyperproliferation in response to anti-CD3 cross-linking.

Immune Dysregulation in Monogenic Inborn Errors of Immunity in Oman: Over A Decade of Experience From a Single Tertiary Center.

Background: Inborn errors of immunity (IEIs) are being recognized as an important cause of morbidity and mortality in communities with a high frequency of consanguinity, such as Oman, and thus recessively inherited conditions. Various monogenic causes of IEI have been recently discovered; however, the disease phenotype may be variable and does not always include infection at presentation, leading to a delay in diagnosis and a poor outcome. It is now well recognized that immune dysregulation manifestations are observed in a significant proportion of patients with IEI and occasionally precede infection.

Disseminated Cryptosporidiosis in an Infant with Non-HIV Pediatric Immunodeficiency: First Case Report from Oman.

is a rare but important pathogen, especially in children with immunodeficiency. Intestinal cryptosporidiosis is well described in immunocompetent and immunocompromised children, but respiratory and disseminated cryptosporidiosis in immunodeficient children is not often reported. We describe an Omani infant with disseminated cryptosporidiosis and failing pharmacological therapy in the context of severe combined immunodeficiency.

A Novel SPINK5 Gene Mutation Associated with Netherton Syndrome in an Omani Patient.

Netherton syndrome (NS) is an autosomal recessive primary immunodeficiency. It is characterised by substantial skin barrier defects and is often misdiagnosed as severe atopic dermatitis or hyper-immunoglobulin E syndrome. Although more than 80 NS-associated pathogenic mutations in the () gene have been reported worldwide, only one has been reported in the Arab population to date.

Biallelic ZNFX1 variants are associated with a spectrum of immuno-hematological abnormalities.

Biallelic changes in the ZNFX1 gene have been recently reported to cause severe familial immunodeficiency. Through a search of our bio/databank with information from genetic testing of >55 000 individuals, we identified nine additional patients from seven families with six novel homozygous ZNFX1 variants. Consistent with the previously described phenotype, our patients suffered from monocytosis, thrombocytopenia, hepatosplenomegaly, recurrent infections, and lymphadenopathy.

The Spectrum of Bacille Calmette-Guérin Diseases in Children-A Decade of Data from Neonatal Vaccination Settings.

In this paper, we present a multicentre record-based descriptive study used to estimate the incidence and characterize the spectrum of confirmed bacille Calmette-Guérin (BCG) vaccine-related disease among children in Oman. This study included all children (age ≤ 14 years) who had culture and/or polymerase chain reaction (PCR)-confirmed BCG disease from January 2006 to December 2018, as identified from Central Public Health Laboratory data and International Classification of Diseases coding of an electronic patient information system. In total, 88 children confirmed to have BCG disease were included in the study, making an average incidence of 9.

Loss of DIAPH1 causes SCBMS, combined immunodeficiency, and mitochondrial dysfunction.

Background: Homozygous loss of DIAPH1 results in seizures, cortical blindness, and microcephaly syndrome (SCBMS). We studied 5 Finnish and 2 Omani patients with loss of DIAPH1 presenting with SCBMS, mitochondrial dysfunction, and immunodeficiency.

Objective: We sought to further characterize phenotypes and disease mechanisms associated with loss of DIAPH1.

Bacillus Calmette-Guérin vaccine-related complications in children in Oman.

Background: Bacillus Calmette-Guérin (BCG) vaccine-related complications are frequently observed in children in Oman. There are a few regional studies on BCG complications, but none from Oman.

Objective: Evaluate the spectrum of BCG-vaccine related complications and immune status in Omani children.

A Decade Experience on Severe Combined Immunodeficiency Phenotype in Oman, Bridging to Newborn Screening.

Introduction: Severe combined immunodeficiency (SCID) results from various monogenic defects that impair immune function and brings on early severe and life-threatening infections. The main stay of treatment for SCID is hematopoietic stem cell transplant (HSCT) with near normal survival at 5 years for an early transplant done at or before the age of 3.5 months of life and the patient is maintained free of infections.

Chronic Q Fever Endocarditis in an Omani Child: The First Pediatric Case Report from Oman.

Q fever endocarditis is the most common presentation of chronic infection of but it rarely occurs in the pediatric age group. We report the first case of Q fever endocarditis in an Omani child. The affected 11-year-old female lives in the Al Batinah governorate in the north of Oman and was known to have congenital heart disease.

Recurrent miscalling of missense variation from short-read genome sequence data.

Background: Short-read resequencing of genomes produces abundant information of the genetic variation of individuals. Due to their numerous nature, these variants are rarely exhaustively validated. Furthermore, low levels of undetected variant miscalling will have a systematic and disproportionate impact on the interpretation of individual genome sequence information, especially should these also be carried through into in reference databases of genomic variation.

A novel truncating mutation in MYD88 in a patient with BCG adenitis, neutropenia and delayed umbilical cord separation.

Mutations in MYD88 cause susceptibility to invasive bacterial infections through impaired signaling downstream of toll-like receptors (TLRs) and IL-1 receptors. We studied a patient presenting with neutropenia, delayed umbilical cord separation, BCG adenitis, andP. aeruginosapneumonia.

Biallelic mutations in AP3D1 cause Hermansky-Pudlak syndrome type 10 associated with immunodeficiency and seizure disorder.

Several types of Hermansky-Pudlak syndromes (HPS) represent a group of immunodeficiency syndromes that feature both leukocyte defects with partial albinism of hair, skin, and eyes. These conditions share defects in genes that encode proteins involved in the biogenesis, function, and trafficking of secretory lysosomes. Mutations in AP3D1 which encode the main subunit AP-3(δ) were recently reported on one individual and led to Hermansky-Pudlak Syndrome type 10 (HPS10; OMIM 617050).

Genetic mutations associated with neonatal diabetes mellitus in Omani patients.

Background: Neonatal diabetes mellitus (NDM) is a rare disorder worldwide where diabetes is diagnosed in the first 6 months of life. However, Oman has a relatively high incidence of NDM.

Methods: In this study, we investigated the genetic etiologies underlying NDM and their prevalence in Oman.

Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a novel mutation.

Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor-containing protein (LRBA) cause immune deficiency and inflammation. Here, we are reporting a novel homozygous mutation in allele in 7-year-old Omani boy, born to consanguineous parents. He presented with type 1 diabetes, autoimmune haematological cytopenia, recurrent chest infections and lymphocytic interstitial lung disease.