Inborn errors of immunity (IEIs) are a heterogeneous group of primarily genetic disorders affecting the immune system, whose diagnosis can be challenging.
To describe the characteristics of a pediatric IEI cohort at a single tertiary center in Santiago, Chile, and to evaluate the impact of a set of systematized interventions (SIs) on diagnosis and management.
We analyzed patients with active follow-up for IEIs as of July 2025. Patients were grouped according to whether they were diagnosed before or after the implementation of the SIs (06/24): inclusion of an immunologist in daily clinical rounds; educational seminars on IEI for healthcare personnel; systematic review of medical records to identify suggestive clinical features; training of primary care centers for timely referral; use of the Jeffrey Modell Foundation (JMF) warning signs.
Eleven patients were included. The mean age at diagnosis was 6.48 years (range: 0.19–15.44 years). Table 1 describes the characteristics of the cohort. After implementing the SIs, there was a tendency to reduce the time from first medical contact to diagnosis (18.61 vs. 0.02 months). Additionally, the overall time from first medical contact to treatment was shortened (22.03 vs. 1.71 months). One asymptomatic case was also identified. Compared to a similar period prior to the implementation of SIs (06/24 to 07/25 vs. 04/23 to 05/24), there was a significant increase in the number of diagnoses (6 vs. 1), including more family member screenings (3 vs. 0) and outpatient diagnoses (4 vs. 1).
This is the first report from our tertiary center in Chile on IEI. These disorders are rare and frequently underdiagnosed; the implementation of a simple set of SIs had a significant impact on improving diagnosis and treatment.
Demographic, genetic, and clinical information
| Patient | Family | Gender | Family history | Deceased relatives from IEI | Consanguinity | Diagnosis | Genetic variant | IUIS group | Initial manifestation | Age at Dx (years) | Outpatient Dx | FMC to Dx (months) | FMC to Tx (months) | IRT | Abx prophylaxis | Other Tx | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Before systematized interventions | |||||||||||||||||
| P1 | 1 | M | No | No | No | CD40L deficiency | CD40LG :c.598A>T; p.Arg200* | I | Infection and failure to thrive | 3.07 | No | 0.03 | 0.20 | Yes | Yes | Alive | |
| P2 | 2 | M | Yes | Yes | No | STAT3-HIES | STAT3 :c.1144C>T; p.Arg382Trp | II | Infection and failure to thrive | 6.25 | No | 74.63 | 74.70 | No | Yes | Alive | |
| P3 | 3 | M | No | No | No | XLA | BTK :c.1558C>T; p.R520X | III | Infection | 4.35 | No | 18.20 | 18.20 | Yes | Yes | Alive | |
| P4 | 4 | M | No | No | No | XLA | BTK :c.894+2dup(splice site) | III | Infection and neutropenia | 0.99 | No | 0.20 | 0.57 | Yes | No | Alive | |
| P5 | 5 | F | Yes | Yes | No | HAE type 1 | Not assessed | VIII | Angioedema | 7.32 | Yes | 0.00 | 16.50 | No | No | On-demand | Alive |
| After systematized interventions | |||||||||||||||||
| P6 | 6 | F | No | No | No | FHL2 | PRF1 :c.445G>A; p.Gly149Ser c.50del; p.Leu17Argfs*34 | IV | HLH | 0.19 | No | 0.00 | 0.00 | No | Yes | CyA pre HSCT | Alive |
| P7 | 7 | M | Yes | No | No | HAE type 2 | Not assessed | VIII | Angioedema | 15.44 | Yes | 0.00 | 3.57 | No | No | On-demand | Alive |
| P8 | 4 | M | Yes | No | No | XLA | BTK :c.894+2dup(splice site) | III | Asymptomatic | 0.33 | Yes | 0.00 | 0.47 | Yes | No | Alive | |
| P9 | 5 | F | Yes | Yes | No | HAE type 1 | Not assessed | VIII | Recurrent abdominal attacks | 8.50 | Yes | 0.00 | 2.17 | No | No | On-demand | Alive |
| P10 | 5 | M | Yes | Yes | No | HAE type 1 | Not assessed | VIII | Angioedema | 14.48 | Yes | 0.00 | 2.17 | No | No | On-demand | Alive |
| P11 | 8 | F | Yes | Yes | No | SLE and SAD | In progress | Not classified yet | Infection | 10.35 | No | 0.10 | 1.87 | No | Yes | Steroids, Aza, HCQ | Alive |
| Patient | Family | Gender | Family history | Deceased relatives from IEI | Consanguinity | Diagnosis | Genetic variant | IUIS group | Initial manifestation | Age at Dx (years) | Outpatient Dx | FMC to Dx (months) | FMC to Tx (months) | IRT | Abx prophylaxis | Other Tx | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Before systematized interventions | |||||||||||||||||
| P1 | 1 | M | No | No | No | CD40L deficiency | CD40LG :c.598A>T; p.Arg200* | I | Infection and failure to thrive | 3.07 | No | 0.03 | 0.20 | Yes | Yes | Alive | |
| P2 | 2 | M | Yes | Yes | No | STAT3-HIES | STAT3 :c.1144C>T; p.Arg382Trp | II | Infection and failure to thrive | 6.25 | No | 74.63 | 74.70 | No | Yes | Alive | |
| P3 | 3 | M | No | No | No | XLA | BTK :c.1558C>T; p.R520X | III | Infection | 4.35 | No | 18.20 | 18.20 | Yes | Yes | Alive | |
| P4 | 4 | M | No | No | No | XLA | BTK :c.894+2dup(splice site) | III | Infection and neutropenia | 0.99 | No | 0.20 | 0.57 | Yes | No | Alive | |
| P5 | 5 | F | Yes | Yes | No | HAE type 1 | Not assessed | VIII | Angioedema | 7.32 | Yes | 0.00 | 16.50 | No | No | On-demand | Alive |
| After systematized interventions | |||||||||||||||||
| P6 | 6 | F | No | No | No | FHL2 | PRF1 :c.445G>A; p.Gly149Ser c.50del; p.Leu17Argfs*34 | IV | HLH | 0.19 | No | 0.00 | 0.00 | No | Yes | CyA pre HSCT | Alive |
| P7 | 7 | M | Yes | No | No | HAE type 2 | Not assessed | VIII | Angioedema | 15.44 | Yes | 0.00 | 3.57 | No | No | On-demand | Alive |
| P8 | 4 | M | Yes | No | No | XLA | BTK :c.894+2dup(splice site) | III | Asymptomatic | 0.33 | Yes | 0.00 | 0.47 | Yes | No | Alive | |
| P9 | 5 | F | Yes | Yes | No | HAE type 1 | Not assessed | VIII | Recurrent abdominal attacks | 8.50 | Yes | 0.00 | 2.17 | No | No | On-demand | Alive |
| P10 | 5 | M | Yes | Yes | No | HAE type 1 | Not assessed | VIII | Angioedema | 14.48 | Yes | 0.00 | 2.17 | No | No | On-demand | Alive |
| P11 | 8 | F | Yes | Yes | No | SLE and SAD | In progress | Not classified yet | Infection | 10.35 | No | 0.10 | 1.87 | No | Yes | Steroids, Aza, HCQ | Alive |
Abx: antibiotic; Aza: azathioprine; CyA: cyclosporine; Dx: diagnosis; F: female; FLH2: familial hemophagocytic lymphohistiocytosis type 2; FMC: first medical contact; HAE: hereditary angioedema; HCQ: hydroxychloroquine; HLH: hemophagocytic lymphohistiocytosis; HSCT: hematopoietic stem cell transplantation; IEI: inborn errors of immunity; IRT: immunoglobulin replacement therapy; IUIS: International Union of Immunological Societies; M: male; SAD: specific antibody deficiency; SLE: systemic lupus erythematosus; STAT3-HIES: STAT3 hyper-IgE syndrome; Tx: treatment; XLA: X-linked agammaglobulinemia.
