Myelin oligodendrocyte glycoprotein antibody-associated disease as a novel presentation of central nervous system autoimmunity in a pediatric patient with Wiskott-Aldrich syndrome

Vivien X Xie; Wilson File; Christina Wiedl; Brant R Ward; Blachy Dávila Saldaña; Michael D Keller; Alexandra B Kornbluh

doi:10.1186/s13223-023-00827-x

Myelin oligodendrocyte glycoprotein antibody-associated disease as a novel presentation of central nervous system autoimmunity in a pediatric patient with Wiskott-Aldrich syndrome

Allergy Asthma Clin Immunol. 2023 Aug 7;19(1):68. doi: 10.1186/s13223-023-00827-x.

Authors

Vivien X Xie¹, Wilson File², Christina Wiedl³, Brant R Ward⁴, Blachy Dávila Saldaña⁵, Michael D Keller⁶, Alexandra B Kornbluh⁷

Affiliations

¹ Department of Neurology, District of Columbia, Children's National Hospital, 111 Michigan Ave NW, Washington, 20010, USA. vxie@childrensnational.org.
² Division of Hematology and Oncology, Eastern Virginia Medical School and Children's Hospital of The King's Daughters, Norfolk, VG, USA.
³ Division of Hematology and Oncology, District of Columbia, Children's National Hospital, Washington, USA.
⁴ Division of Allergy and Immunology, Children's Hospital of Richmond, Virginia Commonwealth University, Richmond, VA, USA.
⁵ Division of Blood and Marrow Transplantation, Children's National Hospital, Washington, DC, USA.
⁶ Center for Cancer and Immunology Research, Division of Allergy and Immunology, Children's National Hospital, Washington, DC, USA.
⁷ Department of Neurology, District of Columbia, Children's National Hospital, 111 Michigan Ave NW, Washington, 20010, USA.

Abstract

Background: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene that leads to increased susceptibility to infections, thrombocytopenia, eczema, malignancies, and autoimmunity. Central nervous system (CNS) autoimmune manifestations are uncommon.

Case presentation: We describe the case of a five-year-old boy with refractory thrombocytopenia and iron deficiency anemia who developed relapsing bilateral optic neuritis. Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) via serum fluorescence-activated cell sorting assay was positive (titer 1:100), confirming a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). At age six, molecular panel testing for genes associated with primary immunodeficiency identified a missense WAS gene variant. He was subsequently found to have decreased WAS protein expression, consistent with a diagnosis of WAS.

Conclusions: This case expands the reported spectrum of CNS autoimmunity associated with WAS and may help to inform long-term therapeutic options.

Keywords: Demyelination; Myelin oligodendrocyte glycoprotein antibody associated disease; Optic neuritis; Wiskott-Aldrich syndrome.