Genetic Causes, Clinical Features, and Survival of Underlying Inborn Errors of Immunity in Omani Patients: a Single-Center Study

• Published in: Journal of clinical immunology 2023-02, Vol.43 (2), p.452-465
• Main Authors: Al-Tamemi, Salem, Al-Zadjali, Shoaib, Bruwer, Zandre, Naseem, Shafiq-Ur-Rehman, Al-Siyabi, Nabila, ALRawahi, Mohammed, Alkharusi, Khalsa, Al-Thihli, Khalid, Al-Murshedi, Fathiya, AlSayegh, Abeer, Al-Maawali, Almundher, Dennison, David
• Format: Article
• Language: English
• Subjects: Autosomal recessive inheritance; Biomedical and Life Sciences; Biomedicine; Cell survival; Consanguinity; Diagnosis; Female; Genetic screening; Genetic Testing; Hematopoietic stem cells; Humans; Immune system; Immunity; Immunodeficiency; Immunologic Deficiency Syndromes - genetics; Immunology; Infectious Diseases; Internal Medicine; Intravenous administration; Male; Medical Microbiology; Morbidity; Original Article; Phagocytes; Phenotype; Phenotypes; Prospective Studies; Quality of Life; Stem cell transplantation
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-022-01394-3

Purpose Early identification of inborn errors of immunity (IEIs) is crucial due to the significant risk of morbidity and mortality. This study aimed to describe the genetic causes, clinical features, and survival rate of IEIs in Omani patients. Methods A prospective study of all Omani patients evaluated for immunodeficiency was conducted over a 17-year period. Clinical features and diagnostic immunological findings were recorded. Targeted gene testing was performed in cases of obvious immunodeficiency. For cases with less conclusive phenotypes, a gene panel was performed, followed by whole-exome sequencing if necessary. Results A total of 185 patients were diagnosed with IEIs during the study period; of these, 60.5% were male. Mean ages at symptom onset and diagnosis were 30.0 and 50.5 months, respectively. Consanguinity and a family history of IEIs were present in 86.9% and 50.8%, respectively. Most patients presented with lower respiratory infections (65.9%), followed by growth and development manifestations (43.2%). Phagocytic defects were the most common cause of IEIs (31.9%), followed by combined immunodeficiency (21.1%). Overall, 109 of 132 patients (82.6%) who underwent genetic testing received a genetic diagnosis, while testing was inconclusive for the remaining 23 patients (17.4%). Among patients with established diagnoses, 37 genes and 44 variants were identified. Autosomal recessive inheritance was present in 81.7% of patients with gene defects. Several variants were novel. Intravenous immunoglobulin therapy was administered to 39.4% of patients and 21.6% received hematopoietic stem cell transplantation. The overall survival rate was 75.1%. Conclusion This study highlights the genetic causes of IEIs in Omani patients. This information may help in the early identification and management of the disease, thereby improving survival and quality of life.