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Jyonouchi. J Transl Genet Genom 2023;7:274-90 Journal of Translational
DOI: 10.20517/jtgg.2023.32
Genetics and Genomics

Review Open Access

Inborn errors of immunity present with
neuropsychiatric symptoms overlapping with

autistic behavioral symptoms

Harumi Jyonouchi 1,2
1
Pediatrics, Saint Peter’s University Hospital, New Brunswick, NJ 08901, USA.
2
Pediatrics, School of Medicine, Rutgers University-Robert Wood Johnson, New Brunswick, NJ 08901, USA.
Correspondence to: Dr. Harumi Jyonouchi, Pediatrics, Saint Peter’s University Hospital, 254 10 Easton Ave., New Brunswick, NJ
08901, USA. E-mail: hjyonouchi@saintpetersuh.com

How to cite this article: Jyonouchi H. Inborn errors of immunity present with neuropsychiatric symptoms overlapping with
autistic behavioral symptoms. J Transl Genet Genom 2023;7:274-90. https://dx.doi.org/10.20517/jtgg.2023.32

Received: 26 Aug 2023 First Decision: 13 Nov 2023 Revised: 7 Dec 2023 Accepted: 15 Dec 2023 Published: 22 Dec 2023

Academic Editor: Sanjay Gupta Copy Editor: Fangyuan Liu Production Editor: Fangyuan Liu

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

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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