Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pediatric Immunology, Ege University Faculty of Medicine, Bornova-İzmir, Turkey.
Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.
The Isil Berat Barlan Center for Translational Medicine, Istanbul Jeffrey Modell Foundation Diagnostic Center for Primary Immune Deficiencies, Istanbul, Turkey.
Uludag University, Medical Faculty, Department of Pediatric Immunology and Rheumatology, Bursa, Turkey.
Department of Pediatric Immunology and Allergy, University of Health Sciences Dr. Behçet Uz Children's Hospital, İzmir, Turkey.
Department of Pediatric Immunology and Allergy, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.
Laboratory of Immunology, Department of Medical Biology, Rouiba Hospital, Algiers, Algeria.
Department of Pediatrics, Mustapha Pacha University Hospital, University of Algiers, Algiers, Algeria.
Department of Medical Immunology, University Hospital Center of Beni Messous, University of Algiers, Algiers, Algeria.
Department of Immunology, Pasteur Institute of Algeria/Faculty of Medicine, Algiers, Algeria.
Institut Pasteur de Tunis, Université Tunis El Manar, Tunis, Tunisia.
Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy of Casablanca, King Hassan II University, Casablanca, Morocco.
Department of Pediatrics, Mansoura University Children's Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Department of Allergy, Al-Rashid Allergy Center, Kuwait University, Kuwait City, Kuwait.
Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.
Department Immunology Research Laboratory, Azerbaijan Medical University, Baku, Azerbaijan.
Allergy and Immunology Division, Pediatrics Department, Sidra Medicine, Doha, Qatar.
Allergy and Immunology Section, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.
Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon.
Internal Medicine and Clinical Immunology, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon.
Jeffrey Modell Foundation (JMF), New York City, NY, USA.
PID Clinical Unit and Laboratory, Department of Dermatology, Semmelweis University, Budapest, Hungary.
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, NY, USA.
Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat 13110, PO Box 24923, Kuwait City, Kuwait. wemh@hotmail.com.
Allergy and Clinical Immunology Unit, Pediatric Department, Al-Sabah Hospital, Kuwait City, Kuwait. wemh@hotmail.com.
Division of Immunology, Boston Children's Hospital and Harvard Medical School, 1 Blackfan Circle, Karp, Bldg, 10th Floor, Boston, MA, 02115, USA. raif.geha@childrens.harvard.edu.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. hassan.abolhassani@ki.se.
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, 14186, Huddinge, Stockholm, Sweden. hassan.abolhassani@ki.se.
Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis.
Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers.
Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG).
Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation.
Keywords: Burden of disease; Epidemiology; Inborn errors of immunity; Molecular diagnosis; Primary immunodeficiency.
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![Fig. 1 The association of rate of inborn errors of immunity (IEI) diagnosis and rate of disability-adjusted life year (DALY) [10] in children within countries from the Middle East and North Africa region](/Images/Figures/37_5052.jpeg)
![Fig. 2 Distribution of different inborn errors of immunity (IEI) entities among different countries in the Middle East and North Africa (MENA) region. PAD, primary antibody deficiency; CID, combined immunodeficiency. Global data has been retrieved from references (for more details, please see Table 2) [2, 9]](/Images/Figures/37_5115.jpeg)
