X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN) disease is due to an inherited defect in immunity from loss-of-function mutations in the magnesium transporter 1 gene (MAGT1). Patients can present as adults with XMEN disease from a delayed diagnosis or lack of genetic diagnosis. Allogeneic stem-cell transplantation is curative in XMEN disease, but the mortality is high, especially in adults. Defective N-glycosylation of platelet glycoproteins impairs platelet aggregation and risks fatal mucosal haemorrhage (such as posterior epistaxis with airway obstruction and haemorrhagic shock requiring intubation) early during post-transplant aplasia. Maintaining a platelet level of at least 30×109/L until engraftment could avoid life-threatening haemorrhage. This is the first report of a successful second allogeneic stem-cell transplant in XMEN disease. Allogeneic stem-cell transplant in adults with XMEN disease should be considered as a curative option in patients with suitable donors.

Arterial embolization therapy is a promising strategy for treating both malignant and benign tumors. However, conventional embolic agents often lack inherent radiopacity and have limited embolizing ability, resulting in difficulty in real-time monitoring during arterial embolization, low postoperative tumor necrosis rate, and high risk of recurrence. In this study, we prepared a liquid metal microsphere with radiopacity by disrupting the surface tension of liquid gallium via ultrasonication. These microspheres have a self-limiting oxide layer on their surface, while their core remains liquid. Drug loading can be achieved by modifying the surface of liquid metal microspheres, and the drug-loaded microspheres are named X-MEN. Owing to their unique physical structure, these liquid metal microspheres exhibit excellent fluidity, viscoelasticity, and deformability. This enables them to navigate through microcatheters and conform tightly to the vessel wall, achieving efficient embolization. These microspheres can remain stable in the target vessel for at least six months, with no observed recanalization. In addition, the radiopacity of these microspheres allows for real-time monitoring during arterial embolization, thereby enabling precise control over the embolization process. Therefore, liquid metal microspheres are a very promising long-acting embolic agent for image-guided arterial embolization.

X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation (XMEN) disease is an inborn error of immunity (IEI) affecting the Magnesium Transporter 1 (MAGT1) gene. In this report, we present the diagnostic odyssey for a patient harboring a novel MAGT1 variant resulting in XMEN disease. A 6y old male child of Caucasian ancestry presented at the immunology clinic in our hospital with a history of recurrent upper respiratory tract infections, as well as significant atopy and viral skin lesions. Genetic testing identified a novel, hemizygous pathogenic variant in the magnesium transporter 1 (MAGT1) gene (c.580dup; p.Ser194Phefs*3). Follow-up testing by flow cytometry revealed the canonical disruption in Natural Killer Group 2D (NKG2D) surface expression on CD8 T cells and NK cells, and clinical testing for congenital disorders of glycosylation (CDG) additionally verified the hallmark defect in glycosylation that underpins XMEN disease. Subsequent in silico analyses using AlphaFold provided an in-depth view of the resulting aberrant protein structural variant and its inability to tether itself to the OST-B complex, a pre-requisite for optimal enzymatic activity of the MAGT1 protein. Disease management included infection control and prophylaxis, steroids and immunotherapy for the patient's asthma and atopy, topical antiviral treatment for the warts and molluscum, as well as biannual EBV load monitoring (the patient is EBV negative). This case illustrates how a synergistic multi-disciplinary team approach established a diagnosis of XMEN disease in a patient with an atypical clinical presentation. This case also highlights a growing trend where established diagnostic tools such as flow-cytometry and genomics can be complemented with newer, sophisticated analytical approaches such as AlphaFold to further elucidate the functionally crippling effects of novel variants described in the setting of IEI.

XMEN disease (X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia) is a rare Inborn Error of Immunity (IEI)characterized by impaired magnesium ion transport due to mutations in the MAGT1 gene, which subsequently affects immune cell function. Timely diagnosis and prompt intervention are essential for improving patient outcomes. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential therapeutic approach to restore MAGT1 function. We report an infant with XMEN who acquired a novel mutation in the MAGT1 gene, presenting recurrent severe skin infections and neutropenia after 6 months of age, which was effectively managed following aggressive anti-infective treatment and HSCT.

The patient was a 46-year-old man with a family history of malignant lymphoma. He presented with bilateral submandibular and cervical lymphadenopathy, which resolved spontaneously. However, approximately one year later, he was admitted to our hospital for treatment of systemic lymph node swelling and bacterial pneumonia. Inguinal lymph node biopsy showed residual lymph follicles with T-zone expansion and numerous Epstein-Barr virus encoding region in situ hybridization (EBER-ISH) positive B-cells. Epstein-Barr virus (EBV) was also detected in the plasma, and EBV encephalitis was diagnosed. Following antibiotic treatment, the lymph node swelling regressed, and the patient was discharged. Based on the characteristic family history, susceptibility to infections, and EBV viremia, we suspected a primary immunodeficiency syndrome. XMEN disease caused by a pathogenic mutation in the magnesium transporter 1 (MAGT1) gene was diagnosed by genetic testing. To the best of our knowledge, no cases of XMEN disease from Japan have been reported in the literature. It is important to consider genetic testing when primary immunodeficiency is suspected.