Inborn errors of immunity present with neuropsychiatric symptoms overlapping with autistic behavioral symptoms

Abstract

Autism spectrum disorder (ASD) is a behaviorally defined syndrome affected by multiple genetic and environmental factors. A wide variety of risk factors for ASD have been identified and many of these affect immune functions. This may not be surprising, since the immune system and the nervous system share common signaling mechanisms and affect each other as a part of the neuroimmune network. The ever-expanding scope of inborn errors of immunity (IEIs) has revealed multiple pathogenic gene variants that manifest overlapping clinical features of common neuropsychiatric diseases, including ASD. These IEIs often cause dysregulated immune activation and resultant chronic inflammation affecting multiple organs. Some IEIs also cause changes in morphogenesis and plasticity of the central nervous system. Such patients often present with a puzzling array of clinical features and some of them may be diagnosed with ASD or other neuropsychiatric conditions. The progress of our understanding of disease mechanisms for IEIs at the molecular levels has led to gene-specific treatment measures in some diseases. In addition, some ASD patients are found to have laboratory findings of neuroinflammation that resemble those seen in IEI patients. This may pave the way for applying specific treatment measures used for IEI patients in such ASD patients. This review focuses on describing IEIs that have overlapping features of ASD. Emphasis is also on IEIs that can be treated by targeting identified disease mechanisms. Such information may be helpful for clinicians who are considering genetic/metabolic workup in ASD patients.

Keywords

Autism spectrum disorder (ASD) / inborn errors of immunity (IEI) / gene mutation-specific treatment / microdeletion syndrome / autoinflammatory syndrome / type 1 interferonopathies

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