Primary Immunodeficiency Diseases in Highly Consanguineous Populations from Middle East and North Africa: Epidemiology, Diagnosis, and Care

Abstract

Middle East and North Africa region (MENA)1 populations are of different ethnic origins. Consanguineous marriages are common practice with an overall incidence ranging between 20 and 50%. Primary immunodeficiency diseases (PIDs) are a group of heterogeneous genetic disorders caused by defects in the immune system that predisposes patients to recurrent infections, autoimmune diseases, and malignancies. PIDs are more common in areas with high rates of consanguineous marriage since most have an autosomal recessive mode of inheritance. Studies of PIDs in the region had contributed into the discovery and the understanding of several novel immunodeficiency disorders. Few MENA countries have established national registries that helped in estimating the prevalence and defining common PID phenotypes. Available reports from those registries suggest a predominance of combined immunodeficiency disorders in comparison to antibody deficiencies seen in other populations. Access to a comprehensive clinical immunology management services is limited in most MENA countries. Few countries had established advanced clinical immunology service, capable to provide extensive genetic testing and stem cell transplantation for various immunodeficiency disorders. Newborn screening for PIDs is an essential need in this population considering the high incidence of illness and can be implemented and incorporated into existing newborn screening programs in some MENA countries. Increased awareness, subspecialty training in clinical immunology, and establishing collaborating research centers are necessary to improve patient care. In this review, we highlight some of the available epidemiological data, challenges in establishing diagnosis, and available therapy for PID patients in the region.

Systematic investigation for underlying causes of recurrent infections in children: surveillance of primary immunodeficiency

“…Although genetic analysis was not the scope of this study, the findings of higher consanguinity and slightly higher rate of male gender in antibody and combined immunodeficiencies reflect the presence of autosomal recessive and X-linked inheritance pattern of PID in our cohort, respectively, as has been reported previously (38,39). These findings are in accordance with other reports from the Middle Eastern region (40) with a high rate of consanguineous marriage, and North of Africa countries (41,42). No patient with a final diagnosis of complement deficiencies or autoinflammatory diseases was recorded in this survey.…”

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis

“…Of note, many of the novel PID gene defects, mainly in autosomal recessive form, have been reported from the Middle East region. Therefore, continuous update on these registries has had a significant impact on our understanding of the pathogenesis of PID and also the function of the immune system [12,13]. Here, we provide a recent update on newly diagnosed Iranian patients with PIDs and integration of molecular diagnostic outcomes based on the latest classification of PIDs by the International Union of Immunological Societies (IUIS) Expert Committee [1].…”

DOCK8 mutation diagnosed using whole-exome sequencing of the dried blood spot-derived DNA: a case report of an Iraqi girl diagnosed in Japan

“…Many of the reported DOCK8- deficient cases were among consanguineous populations, including those of Arabic and Turkish descent [6]. Notably, consanguineous marriages in Middle East countries such as Saudi Arabia, Iraq, Kuwait, Syria and Iran, are exceeding 50% of marriages [16,19,20]. DOCK8 deficiency accounted for a significant proportion (15%) of patients who suffered from combined PID in Kuwait [20].…”