Newborn Screening for SCID, severe T-and B-cell Lymphopenia in Ukraine: a First Analysis of the Results, 2022-2025

Oksana Boyarchuk^1*Halyna Makukh²Alla Volokha³Anastasiia Bondarenko³Nataliia Mytsyk⁴Oksana Barvinska⁴Ivanna Shymanska²Yuliia Pohuliai⁵Mykola Veropotvelyan⁵Anastasia Haviley⁶Marharyta Hurina⁶Yaryna Romanyshyn⁷Maryna Trophymova⁴Iryna Hrabovska⁸Oksana Malko⁹Tetiana Tsanko¹⁰Oksana Tykholaz¹¹Oleksandr Lysytsya⁴Nataliia Samonenko⁴Nataliia Olkhovych⁴

• ¹Ternopil State Medical University, Ternopil, Ukraine
• ²2Department of Regional Center of Neonatal Screening, Lviv Regional Clinical Perinatal Centre, Lviv, Ukraine
• ³Nacional'nij universitet ohoroni zdorov'a Ukraini imeni P L Supika, Kyiv, Ukraine
• ⁴Center of Genetic Diagnostics and Cell Immunotherapy, National Specialized Children’s Hospital “OHMATDYT”, Kyiv, Ukraine
• ⁵Department of Neonatal Screening, Multiregional Center of Medical Genetics and Prenatal Diagnostics named after P.M. Veropotvelyan, Kryvyi Rih, Ukraine
• ⁶Laboratory of Molecular Diagnostics, Kharkiv Specialized Medical Genetics Center – Center for Rare (Orphan) Diseases, Kharkiv, Ukraine
• ⁷Clinic of Pediatric Immunology and Rheumatology, Western Ukrainian Specialized Children's Medical Centre, Lviv, Ukraine
• ⁸Department of Pediatrics Oncohematology, Volyn Regional Territorial Mother and Child Health Care Center, Lutsk, Ukraine
• ⁹Center for Oncohaematology, Immunology and Metabolic Disorders, Rivne Regional Council Municipal Enterprise “Rivne Regional Children’s Hospital”,, Rivne, Ukraine
• ¹⁰Department of Oncohaematology, Municipal Non-Profit Enterprise "Regional Children's Hospital of the Transcarpathian Regional Council",, Uzhhorod, Ukraine
• ¹¹Department of Propedeutics of Pediatric Diseases with Patient Care, National Pirogov Memorial Medical University, Vinnytsia, Ukraine

ABSTRACT Introduction: Severe combined immunodeficiency (SCID) and other profound T-and B-cell lymphopenias are life-threatening conditions that benefit from early diagnosis and treatment. In October 2022, Ukraine launched a nationwide newborn screening (NBS) program for SCID using TREC/KREC/SMA assay, despite ongoing war-related challenges. The aim of this study was to analyze the results of the SCID newborn screening program in Ukraine, evaluate its effectiveness, and outline the current challenges and future directions for its development. Methods: We analyzed data of screened newborns for SCID and related lymphopenias using TREC/KREC/SMA assay from October 2022 to April 2025. The results of lymphocyte flow cytometry values, genetic testing, and clinical management of patients with positive TREC/KREC results were evaluated. Results: Among 398,415 screened newborns, 57 were identified with positive results (32 TREC±KREC and 25 only KREC). The program demonstrated a high diagnostic yield, with an overall referral rate of 0.01%. In total, 18 newborns with inborn errors of immunity were diagnosed due to NBS (7 SCID/leaky SCID and 11 non-SCID). One case of ZAP70 deficiency was missed due to normal levels of T-cells. The incidence of SCID/leaky SCID detected by NBS was 1 in 57,000 live births, and 1 in 49,800 live births when all diagnosed cases, including one initially missed case, were taken into account, which is comparable to data from other countries. All identified by NBS SCID/leaky SCID patients received hematopoietic stem cell transplantation, with a survival rate of 85.7%. Nijmegen breakage syndrome was the most common syndromic cause of non-SCID T-cell lymphopenias (3 cases). The use of KREC assay enabled the first-time identification in Ukraine of B-cell lymphopenias associated with variants in IGLL1 gene. Conclusions: The nationwide newborn screening program in Ukraine demonstrated high sensitivity and specificity in detecting SCID, with a low referral rate and high survival rates among diagnosed patients.