Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naïve Boy Is Associated With a Novel SH2D1A Mutation

Abstract

X-linked lymphoproliferative disease (XLP1) is a combined immunodeficiency characterized by severe immune dysregulation caused by mutations in the SH2D1A/SAP 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 SH2D1A point mutation affecting the start codon. Basal levels of SAP protein seemed to be detectable in CD8+ and CD4+ T- and CD56+ NK-cells of the patient what indicated an incomplete absence of SAP. In conclusion, we could demonstrate a novel SH2D1A mutation leading to deficient SAP protein expression and a rare clinical phenotype of non-EBV associated acute meningoencephalitis with thrombotic occlusive vasculopathy.

Evaluation of pediatric patients with Human Herpes Virus-6 and/or Human Herpes Virus-7 detected in cerebrospinal fluid: a single center experience

“…When laboratory findings were examined, leucocytosis was more common than leukopenia, and the mean CRP value was high, which is expected in bacterial infections and not in viral infections. In addition, the frequency of detection of thrombosis in the cerebral veins in our patients infected with HHV-7 was different what is reported in the literature in terms of HHV-7-related vasculopathies in the paediatric age group [26,39,40]. The detection of HHV-7 in CSF PCR in all patients with cerebral thrombosis was another important finding.…”

“…The development of a PFAPA attack in one of our patients infected with HHV-7 and the development of an oligoarticular JIA attack in another patient raises the possibility that this virus may also be associated with autoimmune and autoinflammatory processes. HHV-7related autoimmune vasculopathies and events are also mentioned in the literature [12,24,26,31,32,[39][40]. Our study contributes to the literature in terms of raising awareness about HHV-7-related vasculopathies and autoimmune processes and highlights the need for multicentre and prospective studies.…”

“…The detection of HHV-7 in CSF PCR in all patients with cerebral thrombosis was another important finding. While HHV-7-related cerebral vasculopathies are reported in adults, there is not enough data in children [26,32,[29][30][31][32][33][34][35][36][37][38][39][40]. Our study makes an important contribution to the literature in this respect.…”