Inborn errors of metabolism underlying primary immunodeficiencies

Area of Science:

• Immunology
• Metabolic disorders
• Genetics

Background:

• Inborn errors of metabolism (IEM) can present with significant immunologic phenotypes, classified as inborn errors of immunity.
• These conditions arise from defects in fundamental cellular processes, including building blocks, energy metabolism, protein modification, and mitochondrial function.
• The resulting multisystemic defects impact both innate and adaptive immunity, leading to diverse immune dysregulations.

Purpose of the Study:

• To review the pathogenesis, diagnosis, and treatment of primary immunodeficiencies (PIDs) that stem from underlying metabolic disorders.
• To highlight the connection between metabolic pathways and immune system integrity.
• To provide a comprehensive overview for clinicians and researchers.

Main Methods:

• Literature review focusing on IEM with immunologic manifestations.
• Analysis of disease mechanisms linking metabolic defects to immune dysfunction.
• Synthesis of current diagnostic approaches and therapeutic strategies.

Main Results:

• Defects in nucleic acids, amino acids, glucose metabolism, glycosylation, and mitochondrial function are common causes of IEM-associated immunodeficiencies.
• These disorders lead to dysregulation across innate and adaptive immune systems.
• A range of treatments, from curative to remission-inducing, are available for specific conditions.

Conclusions:

• Metabolic disorders are an important, often overlooked, cause of primary immunodeficiencies.
• Accurate diagnosis requires consideration of both metabolic and immunologic findings.
• Targeted therapies can significantly improve outcomes for patients with these complex conditions.