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.

SummaryHereditary angioedema (HAE) is a rare disease associated with either a quantitative or qualitative deficiency in C1-inhibitor (C1-INH) or normal C1-INH. HAE with normal C1-INH is associated in 20% of cases with mutations in the gene for factor XII (FXII) or FXII-HAE. A recent review described 41 families, including 14 German and 15 Spanish families. We have constructed a register of French patients and their characteristics. A national survey was launched through the French National Center of Reference for Angioedema (CREAK) to study the clinical, biological and therapeutic characteristics of patients with HAE linked to a mutation of FXII gene. Fifty-seven patients were identified from 24 different families. In most cases they were young women (mean age at diagnosis: 31 years, mean age at first symptom: 21 years, female/male ratio: 76%). Twenty-one per cent of the patients experienced angioedema attacks only during pregnancy or when on oestrogen contraception. Sixty-three per cent had attacks at all times, but they were more severe during these same periods. Male carriers of the mutation were more frequently asymptomatic than females (P 5 0Á003). C1-INH concentrate and icatibant were both effective for treating attacks. The prophylactic use of tranexamic acid led to a 64% decrease in the number of attacks. This is one of the largest series reported of HAE patients with FXII mutation. The therapeutic management appeared to be identical to that of HAE with C1-INH deficiency.

Several sequence changes have been reported in hereditary angioedema patients in intron 2 of the SERPING1/C1NH gene, but their consequences on splicing have not been determined. We examined in cell transfection assays the consequences at the mRNA level of splicing mutations affecting either the +3 or the +5 donor site positions, or the conserved canonical splicing signals of exon 2, using mutant C1 inhibitor minigene constructs. Both intron 2 mutations, c.51+3A>G and c.51+5G>A, resulted in marked exon 2 skipping in these assays, but also yielded a large fraction of normal transcripts. We show that the c.51+3A>G mutation cosegregates with low C1 inhibitor protein levels in one family. Moreover, the second base of exon 2 of the SERPING1/C1NH gene is the site of a polymorphic variant, which has been proposed as a modifier of disease severity. We found that the c.-21C allele at this position yields low but significant levels of exon 2 skipping in transfected Hep G2 or Hep 3B cells, suggesting that this allele may contribute, at the RNA level, to more severe forms of angioedema. Furthermore, we describe a previously not detected alternative splicing of exon 3, found in peripheral blood cell mRNA but not in the liver or in hepatoma cell lines and we show that, in cultured monocytes of a patient carrying the c.51+3A>G mutation, this alternative splicing is shifted from exon 3 exclusion to skipping of both exons 2 and 3. The latter finding suggests that mutations affecting splicing of exon 2 of the SERPING1/C1NH gene may have different consequences in monocytes versus other cell types.

The FXII-HAE is associated with modifiers, for example kinin catabolism enzymes, ACE and CPN, different from those recognized in HAE with C1Inh deficiency.

Introduction Aucune étude antérieure n’a élaboré le profil des patients Algériens hospitalisés pour COVID-19. L’objectif de cette étude était de déterminer le profil clinique, biologique et tomodensitométrique des patients Algériens hospitalisés pour COVID-19. Méthodes Une étude prospective était menée auprès des patients hospitalisés pour COVID-19 (période: 19 mars-30 avril 2020). Les données cliniques, biologiques et radiologiques, le type de traitement reçu et la durée de l’hospitalisation étaient notés. Résultats Le profil clinique des 86 patients atteints de COVID-19 était un homme non-fumeur, âgé de 53 ans, qui était dans 42% des cas en contact avec un cas suspect/confirmé de COVID-19 et ayant une comorbidité dans 70% des cas (hypertension artérielle, diabète sucré, pathologie respiratoire chronique et allergie, cardiopathie). Les plaintes cliniques étaient dominées par la triade «asthénie-fièvre-toux» dans plus de 70% des cas. Les anomalies biologiques les plus fréquentes étaient: syndrome inflammatoire biologique (90,1%), basocytémie (70,8%), lymphopénie (53,3%), augmentation de la lactico-deshydrogénase (52,2%), anémie (38,7%), augmentation de la phosphokinase (28,8%) et cytolyse hépatique (27,6%). Les signes tomodensitométriques les plus fréquents étaient: verre dépoli (91,8%), condensations alvéolaires (61,2%), verre dépoli en plage (60,0%), et verre dépoli nodulaire (55,3%). Un traitement à base de «chloroquine, azithromycine, zinc, vitamine C, enoxaparine, double antibiothérapie et ± corticoïdes» était prescrit chez 34,9% des patients. La moyenne de la durée d’hospitalisation était de 7±3 jours. Conclusion La connaissance des profils des formes modérées et sévères du COVID-19 contribuerait à faire progresser les stratégies de contrôle de l’infection en Algérie.