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Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis.We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant.A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%).The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI.

Severe combined immunodeficiency (SCID) is a heterogeneous group of primary immunodeficiency diseases (PIDs) characterized by a lack of autologous T lymphocytes. This severe PID is rare, but has a higher prevalence in populations with high rates of consanguinity. The epidemiological, clinical, and immunological features of SCIDs in Moroccan patients have never been reported. The aim of this study was to provide a clinical and immunological description of SCID in Morocco and to assess changes in the care of SCID patients over time. This cross-sectional retrospective study included 96 Moroccan patients referred to the national PID reference center at Casablanca Children’s Hospital for SCID over two decades, from 1998 to 2019. The case definition for this study was age

A correction to this paper has been published: https://doi.org/10.1007/s10875-021-01058-8 .

Poikiloderma with Neutropenia (PN) is inherited genodermatosis which results from a biallelic mutation in the USB1 gene (U Six Biogenesis 1). PN, first described in Navajo Native Americans, is characterized by early onset poikiloderma, pachyonychia, palmo-plantar hyperkeratosis, and permanent neutropenia. This condition results in frequent respiratory tract infections during infancy and childhood. From 2011 to 2013, four cases of PN were diagnosed in Morocco. In this paper, we report the first four cases of PN diagnosed in Morocco, out of three unrelated consanguinous families. We investigated the genetic, immunological, and clinical features of four Moroccan patients with PN from three unrelated consanguinous families. Mean age at onset was 3 months and mean age at diagnosis was 7.5 years. The diagnosis of these PN patients was made based on clinical features and confirmed by molecular analysis for three cases. We identified two undescribed homozygous mutations in the USB1 gene: c.609 + 1G>A in two siblings and c.518 T>G(p.(Leu173Arg)) in the other case. This report confirms the clinical and genetic identity of Poikiloderma with Neutropenia syndrome.

World Primary Immunodeficiency Week (WPIW) 2013 ran from 22 to 29th April (www.worldpiweek.org), providing an opportunity to reflect on progress made and the challenges that remain for the primary immunodeficiency diseases (PID) community. In this article, representatives from leading PID societies evaluate the situation and plans for further progress in their respective areas of the world. It is hoped that this situation analysis will prompt further focus and enhanced collaboration on the gaps that remain in the pursuit of promoting early diagnosis and treatment of PIDs.

In today's global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text.

The A-project concept was originally proposed by Prof Aziz Bousfiha during the first IPIC Congress in Estoril, November 2013. This one day training programme was inspired by the European J Project but has been designed to suit African needs in training African health care professionals in the diagnosis and management of primary immunodeficiency disorders. As such, a protocol that governs and guides the execution of this training programme was developed in December 2013 to guide the A-project activities. This protocol was gradually improved to meet the training needs of the majority of continent. It is now proposed that 3 levels of A-project are held to cope with different levels of expertise as follows

Chronic granulomatous disease (CGD) is characterized by an inability of phagocytes to produce reactive oxygen species (ROS), which are required to kill some microorganisms. CGD patients are known to suffer from recurrent bacterial and/or fungal infections from the first year of life onwards. From 2009 to 2013, 12 cases of CGD were diagnosed in Morocco. We describe here these Moroccan cases of CGD.We investigated the genetic, immunological and clinical features of 12 Moroccan patients with CGD from 10 unrelated kindreds.All patients were children suffering from recurrent bacterial and/or fungal infections. All cases displayed impaired NADPH oxidase activity in nitroblue tetrazolium (NBT), dihydrorhodamine (DHR) or 2',7' dichlorofluorescein diacetate (DCFH-DA) assays. Mutation analysis revealed the presence of four different mutations of CYBB in four kindreds, a recurrent mutation of NCF1 in three kindreds, and a new mutation of NCF2 in three patients from a single kindred. A large deletion of CYBB gene has detected in a patient. The causal mutation in the remaining one kindred was not identified.The clinical features and infectious agents found in these patients were similar to those in CGD patients from elsewhere. The results of mutation analysis differed between kindreds, revealing a high level of genetic and allelic heterogeneity among Moroccan CGD patients. The small number of patients in our cohort probably reflects a lack of awareness of physicians. Further studies on a large cohort are required to determine the incidence and prevalence of the disease, and to improve the description of the genetic and clinical features of CGD patients in Morocco.

Primary immunodeficiency diseases (PIDs) comprise at least 176 hereditary disorders that are thought to be individually and collectively rare. The actual prevalence and incidence of PIDs remains unclear, but recent epidemiologic studies have suggested that PIDs are more common than generally thought. Based on these studies, we attempted to estimate the worldwide prevalence and incidence of PIDs.Using data from registries and two recent epidemiologic surveys estimating the frequencies of PIDs, we extrapolated the frequencies reported for certain countries to the populations of continents and of the world.Our upper estimates suggest that six million people may be living with a PID worldwide, whereas only 27,000-60,000 have been identified to date (all national registries and the Jeffrey Modell Centers Network, respectively). For Europe, our upper estimate was 638,000 cases, and 15,052 cases are currently registered (2.27 %). In Africa, up to 902,631 people may have a PID, whereas only 1,016 cases are currently registered. We also found that PIDs were prevalent not only in children, but also in adults, who were strongly underrepresented in registries.Specific, dedicated epidemiologic studies are required, to obtain more realistic statistics for PIDs and to increase the awareness of physicians and public health systems about these diseases. Furthermore, the field of PIDs is continually growing, and this is likely to lead to a revision of the definition of these conditions, potentially increasing estimates of their impact on both adults and children, at the population level.