Neurological findings may be initial presenting symptom in children with inborn errors of immunity

Neurological manifestations in patients with inborn errors of immunity (IEI) may occur during the disease course or, in some cases, represent the initial presenting feature. Increased awareness of these manifestations may facilitate earlier diagnosis and more effective management of IEIs, thereby preventing irreversible neurological morbidity. This study aimed to investigate the relationship between IEI subtypes and neurological involvement and to highlight the role of neurological symptoms in early diagnosis.

This study included patients younger than 18 years who were diagnosed with IEI according to the European Society for Immunodeficiencies diagnostic criteria and followed between 2011 and 2024. Demographic characteristics, neurological manifestations, genetic findings, neuroimaging data, and electroencephalography findings were recorded. Patients were phenotypically classified according to the 2024 International Union of Immunological Societies IEI classification.

A total of 105 patients were included, with a median age at presentation of 48 months (interquartile range: 10-108), and 53.3% were male. The most common IEI category was primary antibody deficiency (35.9%), followed by combined immunodeficiencies with associated or syndromic features (30.5%). Neurological manifestations were present in 34 patients (32.3%). Combined immunodeficiency with associated or syndromic features was the most frequent category among patients with neurological involvement (76.5%). Cognitive and developmental delay was the most common neurological finding. At the time of IEI diagnosis, 88% of patients already had neurological symptoms, and in 44% of cases, neurological complaints were the primary reason for initial hospital admission.

Neurological symptoms may constitute the initial presenting complaint in patients with IEI. Clinicians should remain alert to warning signs suggestive of underlying IEI when evaluating children with neurological findings, as early recognition is crucial for timely diagnosis and optimal management.