Mortality rate and causes of death in inborn errors of immunity: A systematic review and meta-analysis.

BACKGROUND Patients with inborn errors of immunity (IEI) experience severe infectious and non-infectious complications, leading to an increased risk of mortality. Delayed diagnosis or misdiagnosis significantly contributes to the heightened mortality rates observed in IEI patients. OBJECTIVES This study systematically reviews the causes of mortality in IEI patients with a meta-analysis to determine the mortality rate among patients with various IEI. METHODS Embase, ISI Web of Science, PubMed, and Scopus were searched (up to July 2024) using terms related to IEI and mortality. RESULTS A total of 12,581 deceased IEI patients were included, with an overall reported mortality rate of 24.0 % (95 % confidence interval: 23.0-26.0 %) among all published IEI cases. This represents an approximately 27-fold higher mortality rate among IEI patients compared to the mean global mortality rate (24 % vs. 0.874 %). Severe combined immunodeficiency, chronic granulomatous disease, and ataxia-telangiectasia had the highest numbers of reported deceased cases (2304, 962, and 820 cases, respectively). However, familial hemophagocytic lymphohistiocytosis exhibited the highest mortality rate (49.0 %). The most common causes of death were infections, transplant-related mortality and non-infectious pulmonary complications, (3429, 2749, and 1141 cases), respectively. Among infectious causes of death, COVID-19 infection accounted for 10.8 % (370 cases). CONCLUSION This study identifies specific types of IEI with the highest mortality rates and numbers, alongside immune component defects most strongly associated with increased mortality. Patients with immune dysregulation, defects in cellular immunity, and phagocyte function were particularly linked to higher mortality rates, underscoring the urgent need for improved management strategies for these IEIs.

• Publication year

  2025

• Venue

  Mutation research. Reviews in mutation research

• Publication date

  2025-07-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.mrrev.2025.108564PMID 41016093
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Inborn errors of immunity (primary immunodeficiencies)

  2024cited by this paper
• ATM germline pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological malignancies.

  2024cited by this paper
• Survival After Hematopoietic Stem Cell Transplantation in Severe Combined Immunodeficiency (SCID): A Worldwide Review of the Prognostic Variables

  2024cited by this paper
• Reducing Mortality and Morbidity in Children with Severe Combined Immunodeficiency in Switzerland: the Role of Newborn Screening

  2024cited by this paper
• Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis

  2024cited by this paper
• Late effects following hematopoietic cell transplantation for severe combined immunodeficiency: critical factors and therapeutic options

  2024cited by this paper
• Ataxia-telangiectasia clinical trial landscape and the obstacles to overcome

  2023cited by this paper
• Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium.

  2023cited by this paper
• Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment

  2023cited by this paper
• Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee

  2022cited by this paper
• The natural history of ataxia-telangiectasia (A-T): A systematic review

  2022cited by this paper
• Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity, an EBMT IEWP study.

  2022cited by this paper
• Gene therapy for inborn errors of immunity: past, present and future

  2022cited by this paper
• The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity

  2022cited by this paper
• Retrospective, Landmark Analysis of Long-term Adult Morbidity Following Allogeneic HSCT for Inborn Errors of Immunity in Infancy and Childhood

  2022cited by this paper
• Quality of Life and Social and Psychological Outcomes in Adulthood Following Allogeneic HSCT in Childhood for Inborn Errors of Immunity

  2022cited by this paper
• SCID newborn screening: What we've learned.

  2021cited by this paper
• Respiratory Infections in Patients with Primary Immunodeficiency.

  2021cited by this paper
• Multidisciplinary Management of Ataxia Telangiectasia: Current Perspectives

  2021cited by this paper
• Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

  2021cited by this paper
• Haematopoietic Cell Transplantation in Chronic Granulomatous Disease: a Study on 712 Children and Adults.

  2020cited by this paper
• The spectrum of ATM gene mutations in Iranian patients with ataxia‐telangiectasia

  2020cited by this paper
• Two decades of excellent transplant survival for chronic granulomatous disease: a supraregional immunology transplant center report.

  2019cited by this paper
• Role of Allogeneic Hematopoietic Stem Cell Transplant for Chronic Granulomatous Disease (CGD): a Report of the United States Immunodeficiency Network

  2019cited by this paper
• Chronic Granulomatous Disease: Epidemiology, Pathophysiology, and Genetic Basis of Disease

  2018cited by this paper
• Increased burn healing time is associated with higher Vancouver Scar Scale score

  2017cited by this paper
• Evaluation of infectious and non-infectious complications in patients with primary immunodeficiency

  2017cited by this paper
• Incident cancers and late mortality in Australian children treated by allogeneic stem cell transplantation for non‐malignant diseases

  2017cited by this paper
• Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Ped

  2017cited by this paper
• Long-term Survival, Organ Function, and Malignancy after Hematopoietic Stem Cell Transplantation for Fanconi Anemia.

  2016cited by this paper
• A systematic review of studies examining the rate of lung function decline in patients with cystic fibrosis.

  2016cited by this paper
• Incidence and clinical presentation of primary hemophagocytic lymphohistiocytosis in Sweden

  2015cited by this paper
• IgA Deficiency and Risk of Cancer: A Population-Based Matched Cohort Study

  2015cited by this paper
• Lymphoproliferative disease and cancer among patients with common variable immunodeficiency.

  2015cited by this paper
• Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies.

  2015cited by this paper
• Nijmegen Breakage Syndrome: Clinical and Immunological Features, Long-Term Outcome and Treatment Options – a Retrospective Analysis

  2015cited by this paper
• Lung disease in primary antibody deficiency.

  2015cited by this paper
• Common Variable Immunodeficiency: Diagnosis, Management, and Treatment.

  2015cited by this paper
• Pulmonary Manifestations of Primary Immunodeficiency Disorders in Children

  2014cited by this paper
• Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study.

  2014cited by this paper
• Transplantation outcomes for severe combined immunodeficiency, 2000-2009.

  2014cited by this paper
• Risk Factors for Early Fatal Outcomes Among Children with Hemophagocytic Lymphohistiocytosis (HLH): A Single-Institution Case-Series in Vietnam

  2014cited by this paper
• Global overview of primary immunodeficiencies: a report from Jeffrey Modell Centers worldwide focused on diagnosis, treatment, and discovery

  2014cited by this paper
• IgA deficiency and mortality: a population-based cohort study.

  2013cited by this paper
• The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901

  2013cited by this paper
• IgA Deficiency & Mortality: A Population-Based Cohort Study

  2013cited by this paper
• Malignancies are the major cause of death in patients with adult onset common variable immunodeficiency.

  2012cited by this paper
• Epidemiology and Impact of Scarring After Burn Injury: A Systematic Review of the Literature

  2012cited by this paper
• Survival and Predictors of Death Among Primary Immunodeficient Patients: A Registry-Based Study

  2012cited by this paper
• Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme

  2011cited by this paper
• Outcomes following hematopoietic cell transplantation for Wiskott–Aldrich syndrome

  2011cited by this paper
• Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening.

  2011cited by this paper
• Histiocytic disorders: recent insights into pathophysiology and practical guidelines.

  2010cited by this paper
• Evaluation and management of pulmonary disease in ataxia‐telangiectasia

  2010cited by this paper
• Consanguinity and reproductive health among Arabs

  2009cited by this paper
• Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement

  2009cited by this paper
• Predominantly Antibody Deficiencies

  2008cited by this paper
• Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer

  2008cited by this paper
• Nationwide Survey of Hemophagocytic Lymphohistiocytosis in Japan

  2007cited by this paper
• Interstitial lung disease in patients with ataxia‐telangiectasia

  2005cited by this paper
• Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency

  2005cited by this paper
• Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.

  2004cited by this paper
• Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks.

  2004cited by this paper
• Immunodeficiency and infections in ataxia-telangiectasia.

  2004cited by this paper

• No citing papers are available for this paper.