Tehran University of Medical Sciences Immunology and Genetics Journal 2645-4831 8 3 2025 03 15 295 302 Mahsima Shabani Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran; International Hematology/Oncology of Pediatrics Experts (IHOPE), Universal Scientific Education and Research Network (USERN), USA Elham Rayzan Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran; International Hematology/Oncology of Pediatrics Experts (IHOPE), Universal Scientific Education and Research Network (USERN), USA Ido Somekh Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany Christoph Klein Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany Nima Rezaei Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran 2025 03 12 2025 03 15 Background: Congenital cardiac anomalies are considered the most frequent non-hematologic manifestation of Glucose-6-phosphatase 3 (G6PC3) deficiency. Methods: We report a case of G6PC3-deficiency with a novel homozygous frameshift variant (c.911dupC; p.Gln305SerfsTer82), who developed intermittent neutropenia and was diagnosed long after a repair cardiac surgery for patent ductus arteriosus (PDA). To further investigate the importance of immunologic workups in patients with congenital cardiac defects, we provide a literature review on the observed cardiac findings in patients with SCN4. Results: Overall, 78.3% of reported patients had cardiac defects, with more than half of the patients (56%) presenting with ASD. More than half of the patients with ASD required surgical repair, which implies the severity of symptoms. Conclusion: These findings highlight the importance of performing immunologic work-ups in children initially manifesting congenital heart defects. A simple differential cell-blood-count test may prevent future life-threatening disseminated infections, especially in countries with high rates of consanguinity and, subsequently, higher prevalence of primary immunodeficiencies. https://igj.tums.ac.ir/index.php/igj/article/view/206 https://igj.tums.ac.ir/index.php/igj/article/download/206/189