Abstract

The early detection of Severe Combined Immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) prevents fatal outcomes. This study presents the first pilot TREC/KREC newborn screening (NBS) program in southern Kazakhstan, a high-birth-rate region, to establish local reference ranges and assess operational viability. A multiplex real-time PCR assay was used to quantify T-cell (TREC) and kappa-deleting recombination excision circles (KRECs) from dried blood spots of 5000 unselected neonates. Biomarkers were normalized to copies per 106 cells using albumin as a diploid reference gene. Regional 0.5th percentile cut-offs were established (TREC < 3165 copies/106 cells and KREC < 2554 copies/106 cells), and gender and gestational age did not significantly impact biomarker levels. While a low birth weight (≤2500 g) significantly reduced KREC levels, the extreme lower distribution tails remained unaffected, validating the use of universal, unstratified thresholds. Applying these cut-offs yielded an optimal 1.0% initial recall rate. Consistent with global incidence rates, no true positive cases were identified. The established assay and universal percentile cut-offs demonstrate high levels of analytical reliability and demographic stability. This pilot confirms the regional pediatric healthcare infrastructure’s readiness for a routine, population-based NBS program without the need for complex algorithms.

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