Global systematic review of primary immunodeficiency registries

Introduction During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.Peer reviewe

Clinical Features and Types of Von Willebrand Disease in Women with Menorrhagia Referred to Hematology Clinic of Kermanshah

Menorrhagia is the most common symptom that is experienced by women with bleeding disorders. Von Willebrand disease (VWD) is the most common congenital human bleeding disorder that is manifested as a quantitative deficiency in Von Willebrand factor (VWF) or dysfunction of this factor. The frequency of VWD is similar in both men and women. However, VWD is more readily detected in women due to the presence of severe bleeding associated with menstrual cycles and childbirth. The present study was carried out to find the frequency of VWD, its types, and clinical features of the disease among women with menorrhagia who referred to the Hematology Clinic of the Kermanshah University of Medical Sciences. The study comprised 482 women with menorrhagia. After excluding patients with confounding factors, 56 (11.6%) patients were evaluated for inherited bleeding disorders. We detected 31 (55.3%) patients with VWD. Type 3 of VWD was the most frequent subtype (45.1%) followed in frequency by type 2, (32.2%), and type 1 (22.5%). In conclusion, our study indicated that menorrhagia can be the first symptom of VWD. Therefore, rare coagulation disorders should be considered in women with idiopathic menorrhagia, particularly in regions with high rates of consanguinity

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses