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.
