# Syndromic Inborn Errors of Immunity in TREC-Newborn Screening: 5-year Experience from the German Screening Program

## TL;DR

This paper summarizes a 5-year study on German newborns with immune system disorders identified through a screening program, showing how early detection helps with timely treatment and care.

## Contribution

The study is the first comprehensive analysis of syndromic IEI patients identified through TREC-NBS in Germany.

## Key findings

- 64% of patients had primary thymic deficiency, most commonly due to 22q11.2 deletion syndrome.
- Overall survival was 89% with a median follow-up of 32 months.
- Early prophylactic care and timely access to definitive therapies were enabled by the German healthcare system.

## Abstract

TREC-NBS identifies patients with inborn errors of immunity (IEI) and syndromic features, but uncertainty remains regarding their immunological management. To address this, syndromic patients detected by TREC-NBS in Germany between August 2019 and April 2024 were systematically analyzed, including phenotype, treatment, and outcomes. National registries were screened, and data were completed by the treating centres. A total of 77 syndromic patients were identified, with 22 different gene defects found in 72 individuals (93.5%). Primary thymic deficiency was present in 64% (49/77), most commonly due to 22q11.2 deletion syndrome (62%). Common clinical features included congenital heart disease (57%), facial/skeletal abnormalities (53%), and neurological symptoms (36%). Definitive treatments were provided promptly in eligible patients, including 6 thymus transplants and 6 hematopoietic stem cell transplants (HSCT). A watch-and-wait approach was applied to the remaining patients, with 34% (22/65) receiving prophylactic treatment. Recovery of CD3 + T-cell counts was limited to a minority. Overall survival was 89%, with a median follow-up of 32 months (range 0.5–60). To conclude, this is the first comprehensive study of syndromic IEI patients identified through TREC-NBS. The findings show that the German healthcare system enables both early prophylactic care and timely access to definitive therapies. Moving forward, interdisciplinary collaboration will be key to developing evidence-based management guidelines for this challenging patient group.

The online version contains supplementary material available at 10.1007/s10875-026-01995-2.