Expanded newborn screening for inborn errors of metabolism in Isfahan Province: the first two-year report from Central Iran

Abstract

Abstract Background Inborn errors of metabolism cause significant infant morbidity and mortality. Birth prevalence is elevated in the Eastern Mediterranean region, influenced by consanguinity. This study presents the first findings of an expanded newborn screening program for IEMs in Isfahan Province, Central Iran. In this cross-sectional study (2023–2025), 71,004 neonates were screened via tandem mass spectrometry (MS/MS) of dried blood spots for 50 metabolic disorders. Positive cases underwent confirmatory testing. Data on demographics and consanguinity were analyzed. Results From 71,004 newborns, 48 cases were confirmed, corresponding to a prevalence of 67.6 per 100,000 live births, including organic acid, amino acid, and fatty acid oxidation disorders. The most frequent disorders included Short-chain acyl-CoA dehydrogenase (SCAD) deficiency, benign hyperphenylalaninemia (HPA), and 2-Methylbutyryl-CoA dehydrogenase (SBCAD) and 3-Methylcrotonyl-CoA carboxylase (3MCC) deficiencies. Consanguinity was a major risk factor, present in 56.3% of cases (Relative Risk = 2.05). All mortality (10.4%) occurred in the organic acid disorder group. Birth prevalence was highest in smaller towns (e.g., Khansar: 384.6/100,000). Conclusion The high prevalence of IEMs in Isfahan, linked to consanguinity and a distinct disorder profile, underscores the critical importance of expanded NBS. The findings advocate for integrated public health strategies, including genetic counseling and targeted screening, to reduce the disease burden in this region.