QATAR NATIONAL EXPANDED METABOLIC NEWBORN SCREENING PROGRAM: INCIDENCE AND OUTCOMES

Abstract

Background: Newborn screening (NBS) is an essential public health strategy that aims to detect and diagnose inborn errors of metabolism (IEMs) in infants shortly after birth, typically through a minimally invasive heel prick procedure. The timely identification provided by NBS is significant due to the potential asymptomatic nature of many metabolic conditions at birth and which, if left untreated, can result in significant health complications or developmental impediments. Aim: We aimed to investigate the incidence of the core IEMs screened by the Qatar National Newborn Screening Program (QNNSP). Methodology: A retrospective cohort study analyzed NBS cases derived from the QNNSP database from 2010 to 2023. Detailed chart review was conducted while adhering to stringent inclusion and exclusion criteria. A total of 351,233 newborns were initially screened. The incidence was calculated for 20 IEMs for a total of 324 cases included and it was correlated with demographics, consanguinity, and family history. In addition, genetic testing outcomes for IEMs were investigated to assess the diagnostic yield of different tests. Results: This study revealed a significantly high incidence of 20 IEMs detected by NBS in Qatar from 2010 to 2023. The total number of true positive (TP) cases diagnosed with an IEM was 324 newborns. Among the 20 IEMs screened for, Classical Homocystinuria (HCU) was the most frequently detected disorder, with a cumulative incidence of 1:6754 live births. Biotinidase deficiency followed with a cumulative incidence of 1:7805. Isovaleric acidemia was one of the least detected with a cumulative incidence of 1:117078. The study found that aminoacidopathies were the most prevalent category of IEMs, followed by fatty acid oxidation disorders, organic acidurias, biotinidase deficiency, and urea cycle disorders. The study also analyzed the diagnostic yield of genetic testing for IEMs, with targeted variant testing and single gene testing being most effective. Conclusion: NBS is essential for the early detection and treatment of metabolic disorders, thus for reducing morbidity and mortality. Our study reveals a high incidence of 20 Inborn IEMs, notably classical HCU linked to a founder variant. Amnioacidopathies were most prevalent, emphasizing the importance of NBS programs for timely management. Genetic testing showed a high diagnostic yield of 87%, underscoring its utility, with targeted and single-gene tests being most utilized. Further research on specific pathogenic variants is recommended for better understanding and inclusion in premarital screening.