{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:01:44Z","timestamp":1781654504890,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>X-linked lymphoproliferative disease (XLP1) is a combined immunodeficiency characterized by severe immune dysregulation caused by mutations in the <jats:italic>SH2D1A\/SAP<\/jats:italic> gene. Loss or dysfunction of SH2D1A is associated with the inability in clearing Epstein-Barr-Virus (EBV) infections. Clinical manifestation is diverse and ranges from life-threatening hemophagocytic lymphohistiocytosis (HLH) and fulminant infectious mononucleosis (FIM) to lymphoma and antibody deficiency. Rare manifestations include aplastic anemia, chronic gastritis and vasculitis. Herein, we describe the case of a previously healthy eight-year old boy diagnosed with XLP1 presenting with acute non-EBV acute meningoencephalitis with thrombotic occlusive vasculopathy. The patient developed multiple cerebral aneurysms leading to repeated intracerebral hemorrhage and severe cerebral damage. Immunological examination was initiated after development of a susceptibility to infections with recurrent bronchitis and one episode of severe pneumonia and showed antibody deficiency with pronounced IgG1-3-4 subclass deficiency. We could identify a novel hemizygous <jats:italic>SH2D1A<\/jats:italic> point mutation affecting the start codon. Basal levels of SAP protein seemed to be detectable in CD8<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup> T- and CD56<jats:sup>+<\/jats:sup> NK-cells of the patient what indicated an incomplete absence of SAP. In conclusion, we could demonstrate a novel <jats:italic>SH2D1A<\/jats:italic> mutation leading to deficient SAP protein expression and a rare clinical phenotype of non-EBV associated acute meningoencephalitis with thrombotic occlusive vasculopathy.<\/jats:p>","DOI":"10.3389\/fimmu.2021.747738","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T06:47:11Z","timestamp":1639982831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Na\u00efve Boy Is Associated With a Novel SH2D1A Mutation"],"prefix":"10.3389","volume":"12","author":[{"given":"Jolanda","family":"Steininger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Rossmanith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph B.","family":"Geier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Leiss-Piller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Thonhauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes 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