Background:

Inborn errors of immunity (IEIs) are rare genetic disorders affecting immune development and function. Their diagnosis remains challenging because genotype–phenotype correlations are highly variable: a single gene defect may cause diverse phenotypes, whereas similar clinical presentations may result from different genetic abnormalities. Genetic diagnosis is therefore essential for accurate classification, prognosis, treatment planning, and family counseling.

Methods:

This descriptive cross-sectional study included pediatric patients with genetically confirmed IEIs who were followed and treated at Children’s Hospital 1, Ho Chi Minh City, Vietnam, from 2013 to 2025. Demographic, clinical, immunological, genetic, and treatment-related data were retrospectively collected from medical records. Genetic variants were identified using Sanger sequencing, fluorescence in situ hybridization, whole-exome sequencing, and copy-number variant analysis when indicated. Disease groups were classified according to the updated IUIS classification.

Results:

A total of 121 pediatric patients with genetically confirmed IEIs were included. Antibody deficiencies and combined immunodeficiencies were the most common categories, each accounting for approximately 25% of cases. Forty percent of patients presented with infections before 6 months of age, and severe vaccine-related complications, including systemic tuberculosis after routine immunization, were observed. Clinical manifestations were not restricted to infections; autoimmune cytopenias and lymphoproliferation were also important warning signs. Lymphopenia and absence of thymic shadow helped identify severe IEI phenotypes. Whole-exome sequencing and copy-number variant analysis improved genetic diagnosis, with 19 previously unreported variants detected. Overall, 51 mutations, accounting for 51.5%, were large deletions, splicing, frameshift, or nonsense variants. Mortality was highest among patients with cellular and humoral immunodeficiencies, probably due to limited access to hematopoietic stem cell transplantation for IEI patients in Southern Vietnam. Relatively high mortality in predominant antibody deficiency may be related to the limited availability of prophylactic intravenous immunoglobulin in Vietnam before 2020.

Conclusion:

Genetic diagnosis is indispensable for managing pediatric IEIs, as treatment and prognosis vary substantially across molecular subgroups. Integrating clinical recognition, immunological assessment, and complementary genetic approaches supports earlier diagnosis and improved care.

Dr. Phan Nguyen Lien Anh is a pediatric hematologist at the Department of Hematology, Children’s Hospital 1, Ho Chi Minh City, Vietnam, where she has worked since 2006. She has also served as a lecturer at the School of Medicine, Vietnam National University Ho Chi Minh City, since 2015.She graduated as a medical doctor in 2006 and obtained her Master’s degree in Hematology in 2013 and PhD in Hematology in 2023 from the University of Medicine and Pharmacy at Ho Chi Minh City. She has undertaken advanced clinical and research training in Texas, USA, and Tokyo, Japan.Her research focuses on pediatric hematological disorders, particularly primary immunodeficiency diseases and inborn errors of immunity. She received an award for one of the three best submitted abstracts at IPIC 2017 in Dubai.