Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population

Al‐Herz, Waleed; Chou, Janet; Delmonte, Ottavia M.; Massaad, Michel J.; Bainter, Wayne; Castagnoli, Riccardo; Klein, Christoph; Bryceson, Yenan T.; Geha, Raif S.; Notarangelo, Luigi D.

doi:10.3389/fimmu.2018.03146

Cited by 41 publications

(23 citation statements)

References 40 publications

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“…In highly consanguineous populations, AR PIDs represent 70-90% of cases (32,33). Interestingly-though the Russian population is very heterogeneous, with low numbers of consanguineous marriages (45 families, 1.9%)-AR genetic defects comprised 30% of all defects described in the cohort, with 40% of these being homozygous for the respective mutations.…”

Section: Discussionmentioning

confidence: 99%

Primary Immunodeficiencies in Russia: Data From the National Registry

et al. 2020

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Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages. Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs-in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive. Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Primary Immunodeficiencies in Russia: Data From the National Registry

et al. 2020

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“…Autoantibodies testing, nitro blue tetrazolium dye test (NBT) or dihydrorhodamine (DHR) and complement hemolytic activity (CH50/100) with specific complement component were done when needed using the standard techniques. Genetic testing was done as described previously (19).…”

Section: Methodsmentioning

confidence: 99%

“…They provided an invaluable source of information about the natural history and outcome of specific diseases and documented variabilities between different populations (15–18). They have supported research on the genetic, molecular, and physiological basis of PID (19, 20). They can be used to support clinical trials and translational research to improve quality of care, quality of life, and survival.…”

Section: Introductionmentioning

confidence: 95%

The Kuwait National Primary Immunodeficiency Registry 2004–2018

et al. 2019

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Objective: To present the report from the Kuwait National Primary Immunodeficiency Registry between 2004 and 2018. Methods: The patients were followed prospectively between January 2004 and December 2018 and their collected data included sociodemographic, diagnosis, clinical presentation, laboratory tests, and treatment. Results: A total of 314 PID patients (165 males and 149 females) were registered during the study period. Most of the patients ( n = 287, 91.4%) were Kuwaiti nationals and the prevalence among Kuwaitis was 20.27/100,000 with a cumulative incidence of 24.96/100,000 Kuwaitis. The distribution of the patients according to PID categories was as follow: immunodeficiencies affecting cellular and humoral immunity, 100 patients (31.8%); combined immunodeficiencies with associated syndromic features, 68 patients (21.7%); predominantly antibody deficiencies, 56 patients (17.8%); diseases of immune dysregulation, 47 patients (15%); congenital defects of phagocyte number or function, 20 patients (6.4%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 22 patients (7%). The mean age of the patients at onset of symptoms was 26 months while the mean age at diagnosis was 53 months and the mean delay in diagnosis was 27 months. Most of the patients ( n = 272, 86%) had onset of symptoms before the age of 5 years. Parental consanguinity rate within the registered patients was 78% and a positive family history of PID was noticed in 50% of the patients. Genetic testing was performed in 69% of the patients with an overall diagnostic yield of 90%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by an autosomal recessive pattern. Intravenous immunoglobulins and stem cell transplantation were used in 58% and 25% of the patients, respectively. There were 81 deaths (26%) among the registered patients with a mean age of death of 25 months. Conclusions: PID is not infrequent in Kuwait and the reported prevalence is the highest in the literature with increased proportion of more severe forms. Collaborative efforts including introduction of newborn screening should be implemented to diagnose such cases earlier and improve the quality of life and prevent premature deaths.

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“…(17.1%), Among patients molecular diagnosis was observed in 40.2% and parental consanguinity was recorded in 19.4%[34][35][36].During the last decade, other Asian PID cohorts have been reported containing fewer patients each. Al-Herz et al in 2019, published a registry report of 314 PID patients in Kuwait with the highest genetically solved rate of 69.1% with 78.0% paternal consanguinity (prevalence of PID 20.2 in 100000, predominantly antibody immunodeficiency of 17.8%)[37][38][39]. In 2013, Ehlayel et al have reported a single-center registry of 131 pediatric PID patients from Qatar with the lowest number of classical PID diseases and only 23.7% predominant antibody deficiency (prevalence of PID of 1.1 per 100000 children, genetic diagnosis of 36.6%, parental consanguinity of 61.1%)[40].…”

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confidence: 99%

Global systematic review of primary immunodeficiency registries

Abolhassani

Azizi

Sharifi

et al. 2020

Expert Review of Clinical Immunology

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100

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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.

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Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population

Cited by 41 publications

References 40 publications

Primary Immunodeficiencies in Russia: Data From the National Registry

Primary Immunodeficiencies in Russia: Data From the National Registry

The Kuwait National Primary Immunodeficiency Registry 2004–2018

Global systematic review of primary immunodeficiency registries

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