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Page 285 Jyonouchi. J Transl Genet Genom 2023;7:274-90 https://dx.doi.org/10.20517/jtgg.2023.32

Figure 1. Possible mechanisms of neuropsychiatric symptoms in inborn errors of immunity. Examples of IEIs shown in the figure are
known to exhibit neuropsychiatric symptoms overlapping with ASD behavioral symptoms.

COVID-19. In that regard, in older ASD subjects with sudden worsening behavioral symptoms, the
possibility of phenocopies of IEIs may be kept in mind as a possible pathogenesis.

CONCLUSION
In this review, we have summarized IEIs that present with predominant neuropsychiatric symptoms,
secondary to neuroinflammation and impaired neuronal development caused by pathogenic variants of
genes/deletion of genes as summarized in Figure 1. These conditions can be manifested by microdeletion,
genes affecting chromatin remodeling, and those affecting key signaling molecules shared by both the
immune and nervous systems. It should be noted that both the development of autoantibodies against key
mediators and/or somatic mutations of key genes may also cause clinical symptoms similar to those seen in
patients with IEIs, although these patients tend to present later in life. Some patients with IEIs may initially
be diagnosed with ASD, as we have experienced in our clinic. Clinicians need to be aware of the clinical
features of IEIs that may overlap with ASD clinical presentation. It is also important to make use of the
various genetic tests and treatment measures that are currently available for specific gene mutations.
Research in these areas is rapidly expanding, and it will be important to keep up to date on the latest
information. In addition, if ASD patients present with similar immune abnormalities as found in those with
IEIs, immunomodulating agents targeting specific pathways affected by such gene mutations may be
applicable, expanding the scope of treatment options.