XMEN Disease Associated with Recurrent Autoimmune Cytopenias and EBV-Positive Hodgkin Lymphoma: A Case Report
Year: 2025
Type: article
Study design: Case Report
Abstract: To the editor, X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) is a rare primary immunodeficiency caused by mutations in the magnesium transporter 1 (MAGT1) gene [1,2].Due to its rarity and variable clinical course, each case offers valuable insight into this complex condition.A 29-year-old male presented with fever, jaundice, and fatigue.He had a childhood history of idiopathic thrombocytopenic purpura (ITP) and surgery for patent ductus arteriosus.Laboratory tests showed severe anemia (Hb: 4.6 g/dL), mild thrombocytopenia, indirect hyperbilirubinemia, elevated lactate dehydrogenase, C-reactive protein (CRP), and undetectable haptoglobin.The direct Coombs test was negative, and schistocytes were noted on peripheral smear.Thrombotic microangiopathy (TMA) was suspected, but paroxysmal nocturnal hemoglobinuria (PNH) and ADAMTS13 tests were normal.He received plasmapheresis and corticosteroids without benefit.Eculizumab was initiated for suspected atypical hemolytic uremic syndrome (aHUS), leading to hematologic improvement.Bone marrow biopsy showed erythroid hyperplasia with dyserythropoiesis.Computed tomography (CT) examination revealed pathologic axillary lymphadenopathy.Biopsy confirmed EBV-positive nodular lymphocyte predominant Hodgkin lymphoma (Stage 3A), treated with six cycles of R-CHOP, achieving remission.About 2.5 years after the initial presentation, he developed Coombs-positive autoimmune hemolytic anemia (AIHA) with thrombocytopenia.Steroids were ineffective; eltrombopag and rituximab were given.Cytomegalovirus (CMV) reactivation was treated with ganciclovir.Rituximab resolved cytopenias.Approximately 2 years later, severe hemolysis recurred after cefprozil.Rituximab was resumed but paused due to CMV reactivation, which was managed with valacyclovir.About 7 months later, hemolytic anemia relapsed.Azathioprine was started.Thrombocytopenia recurred with infections but responded to intravenous immunoglobulin (IVIG).Due to persistent EBV DNA positivity, as determined by PCR, and thrombocytopenia, eltrombopag was reinitiated.The summary of the treatment course is presented in Figure 1 .Recurrent cytopenias and frequent infections prompted an evaluation for underlying immunodeficiency.Serum immunoglobulin levels and subclasses were decreased (IgG1: 3.4 g/L; IgG2: 1.46 g/L).Family history revealed that the patient's brother had developed gait disturbance, ataxia, and dysarthria following a COVID-19 infection at the age of 26.Genetic analysis of the brother identified a hemizygous X-linked MAGT1 mutation and a heterozygous autosomal dominant COL4A1 mutation.The asymptomatic mother was heterozygous for the same MAGT1 variant.Genetic testing of the patient confirmed a hemizygous MAGT1 mutation (Figure 1).Flow cytometry revealed a CD4/CD8 ratio of 1.1.Serum magnesium concentrations in our case were consistently within normal limits.Hemoglobin and platelet counts returned to normal without further eltrombopag therapy.No evidence of lymphoma recurrence was observed.The patient was initiated on IVIG therapy every 21 days and placed under regular follow-up.Although the diagnostic criteria for XMEN disease have not yet been fully standardized, they can be summarized based on reported cases in the literature and current clinical guidelines.The diagnosis of XMEN disease is based on the identification of a loss-of-function mutation in the MAGT1 gene, which is located on the X chromosome.Hemizygous mutations are typically seen in males, while heterozygous female carriers are usually asymptomatic.Immunological findings often include CD4+ T-cell lymphopenia, impaired T-cell activation, decreased intracellular magnesium levels, and reduced surface expression of the NKG2D receptor on CD8⁺ T cells and NK cells [1].Clinically, affected individuals may present with persistent or chronic EBV viremia, EBV-related lymphoproliferative disorders , recurrent infections and autoimmune cytopenias[3].Additional features may include dysgammaglobulinemia, lymphadenopathy, and splenomegaly.A decreased CD4/CD8 ratio and u n c o r r e c t e d p r o o f
Source: Turkish Journal of Hematology
Authors: Zehra Akşit Bozkına, Nur Soyer
Institution: Ege University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4412492530