Consensus Middle East and North Africa Registry on Inborn Errors of Immunity
Authors: Aghamohammadi Asghar , Rezaei Nima , Yazdani Reza , Delavari Samaneh , Kutukculer Necil , Topyildiz Ezgi , Ozen Ahmet , Baris Safa , Karakoc-Aydiner Elif , Kilic Sara Sebnem , Kose Hulya , Gulez Nesrin , Genel Ferah , Reisli Ismail , Djenouhat Kamel , Tahiat Azzeddine , Boukari Rachida , Ladj Samir , Belbouab Reda , Ferhani Yacine , Belaid Brahim , Djidjik Reda , Kechout Nadia , Attal Nabila , Saidani Khalissa , Barbouche Ridha , Bousfiha Aziz , Sobh Ali , Rizk Ragheed , Elnagdy Marwa H. , Al-Ahmed Mona , Al-Tamemi Salem , Nasrullayeva Gulnara , Adeli Mehdi , Al-Nesf Maryam , Hassen Amel , Mehawej Cybel , Irani Carla , Megarbane Andre , Quinn Jessica ,   MENA-I. E. I. Study Group, Chavoshzadeh Zahra , Mahdaviani Seyed Alireza , Nabavi Mohammamd , Tavakol Marzieh , Behniafard Nasrin , Momen Tooba , Azizi Gholamreza , Bemanian Mohammad Hassan , Arshi Saba , Molatefi Rasol , Sherkat Roya , Shirkani Afshin , Amin Reza , Aleyasin Soheila , Faridhosseini Reza , Jabbari-Azad Farahzad , Ahanchian Hamid , Khoshkhui Maryam , Shafiei Alireza , Kalantari Arash , Mohammadzadeh Iraj , Ghaffari Javad , Cheraghi Taher , Mansouri Mahboubeh , Mesdaghi Mehrnaz , Babaie Delara , Eslamian Mohammad Hossein , Dabbaghzadeh Abbas , Tavassoli Mahmoud , Ghasemi Ramin , Kalmarzi Rasoul Nasiri , Mortazavi Seyed Hamidreza , Kashef Sara , Esmaeilzadeh Hossein , Tafaroji Javad , Khalili Abbas , Zandieh Fariborz , Sadeghi-Shabestari Mahnaz , Darougar Sepideh , Behmanesh Fatemeh , Akbari Hedayat , Zandkarimi Mohammadreza , Abolnezhadian Farhad , Fayezi Abbas , Torabizadeh Mehdi , Moghtaderi Mojgan , Soheili Habib , Ahmadiafshar Akefeh , Shakerian Behzad , Sajedi Vahid , Taghvaei Behrang , Safari Mojgan , Heidarzadeh Marzieh , Ghalebaghi Babak , Fathi Seyed Mohammad , Darabi Behzad , Darabi Kian , Bazregari Saeed , Bazargan Nasrin , Fallahpour Morteza , Khayatzadeh Alireza , Bashardoust Bahram , Sadri Homa , Zamani Mohammadali , Mohsenzadeh Azam , Ebrahimi Sarehsadat , Ghaemi Reza , Mehrjerdi Fatemeh Zare , Sharafian Samin , Nabavizadeh Seyed Hesamodin , Baniadam Leila , Salari Fereshteh , Rekabi Mahsa , Vosughimotlagh Ahmad , Tafakoridelbari Mitra , Pourvali Ali , Rezaei Arezou , Hamidieh Amir Ali , Shariat Mansoureh , Gharagozlou Mohammad , Movahedi Masoud , Parvaneh Nima , Karaca Neslihan Edeer , Aksu Guzide , Eltan Sevgi Bilgiç , Kasap Nurhan , Kolukisa Burcu , Sefer Asena Pınar , Yalcin Ezgi , babayeva Roya , Mahammed Lydia Lamara , Al-Khabaz Ahmad , Maródi László , Modell Vicki , Modell Fred , Al-Herz Waleed , Geha Raif S. , Abolhassani Hassan 
Published: May 2021

Abstract
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.