D1.327 - Genetic Analysis of Children with Suspected Immunodeficiency: Mimickers of Inborn Errors of Immunity

Inborn errors of immunity (IEI) constitute a heterogeneous group of disorders with diverse clinical manifestations. In this study, we evaluated genetic testing outcomes in patients with suspected IEI, focusing on IEI-related, non-immunological, and uncertain variants.

Between January 2020-January 2025, 91 patients aged 0–18 years who underwent genetic testing due to clinical suspicion of IEI at our Pediatric Immunology and Allergy Clinic were retrospectively analyzed. Demographic data, clinical features, immunological profiles, genetic results were reviewed, including single-gene sequencing, fluorescence in situ hybridization (FISH), targeted gene panels (TGP), and whole-exome sequencing (WES). Patients analyzed by next-generation sequencing (NGS) were classified into three categories according to detected variants: IEI-related, non–IEI-related, and disease causing variant not detected.

A total of 79 patients underwent NGS-based genetic testing. The mean age was 4.37±5.09 years. WES was performed in 40 patients (50.6%) and TGP in 39 (49.4%). Pathogenic variants linked to IEI-related were detected in 28 patients (35.4%), whereas non–IEI-related pathogenic variants were identified in 12 (15.2%). The remaining 39 patients (49.4%) disease causing variant not detected. The diagnoses of patients carrying pathogenic variants unrelated to IEI included primary ciliary dyskinesia, Ellis–van Creveld syndrome, desmoglein-1 deficiency, and others. 

Our study highlights the importance of genetic testing in the differential diagnosis of IEI and provides evidence supporting its role in identifying mixed IEI phenotypes. A multidisciplinary approach combined with comprehensive genetic evaluation is crucial for the early diagnosis and effective management of both IEI-related and non–IEI-related disorders.