When Metabolism Meets Immunity: Inborn Errors of Metabolism Mimicking Primary Immunodeficiencies—A Case Series

Several inborn errors of metabolism (IEMs) are known to affect immune function; the latter may arise from disruptions in metabolic pathways critical to immune cell development or from accumulation of toxic metabolites that impair immunity. This overlap can complicate diagnosis and management. We present seven patients with IEMs initially suspected of having inborn errors of immunity (IEIs) to highlight the phenotypic intersections between these disorders. All patients were referred for immunological evaluation due to recurrent infections, cytopenias, or abnormal immune profiles. Each was ultimately diagnosed with an IEM known to affect immune function. Results • Purine nucleoside phosphorylase deficiency: A 4-year-old female with CMV infection, seizures, and lymphopenia was diagnosed with this T cell defect associated with purine metabolism. Good clinical response with intravenous immunoglobulin, oral prednisolone, folic acid, vitamin B, and antiviral. • Propionic acidemia: Three patients presented with early-onset sepsis or viral infections. Immunologic findings included hypogammaglobulinemia, lymphopenia (particularly affecting B and natural killer cells), and neutropenia. Treated with carglumic acid, levocarnitine, protein-rich diet, and replacement immunoglobulin. • Transcobalamin II deficiency: Two patients had recurrent infections, cytopenias, and global lymphopenia. One showed hypogammaglobulinemia. Good response with intramuscular B12 vitamin and folic acid. • Thymidine phosphorylase deficiency: A 17-year-old male presented with ophthalmoparesis, severe abdominal pain, and angiographic images resembling vasculitis, with negative autoantibodies and poor response to immunosuppression. He died a few weeks after liver transplantation. Conclusion This series underscores the immunologic manifestations of IEMs, which can mimic IEIs and complicate diagnosis. Recognizing the bidirectional overlap is crucial: immune evaluation may uncover an underlying metabolic disorder, while persistent infections or immune alterations in IEMs warrant thorough immunological assessment. Immunologic interventions like immunoglobulins, antibiotic prophylaxis, vaccines, etc. may help to reduce the infectious burden in IEMs and improve quality of life. Timely diagnosis and comprehensive management are crucial for both groups of diseases.