Immune dysregulation syndrome with cytotoxic T‐lymphocyte antigen 4 mutation showing multiple central nervous system lesions

Background Haploinsufficiency of cytotoxic T‐lymphocyte antigen 4 (CTLA4) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and diverse autoimmune disorders. Although central nervous system lesions have been described in patients with CTLA4 insufficiency, there have been few reports in the field of neurology. Case presentation A 23‐year‐old man was referred to Saga University Hospital (Saga, Japan) with dizziness and abnormal head magnetic resonance imaging showing hyperintensity in the left cerebellar hemisphere. He was diagnosed with immune thrombocytopenia and hypogammaglobulinemia at age 8 years. He had repeated mild upper respiratory infections. Neurological events had occurred four times, with a long spinal lesion extending over three vertebral segments. High‐dose intravenous methylprednisolone was effective for acute attacks, and low‐dose prednisolone prevented relapses for 7 years. When he reached the age of 37 years, he developed severe diarrhea and immune cytopenia, and lost 6 kg in half a year. It was suspected that the patient had primary immunodeficiency due to his history of recurrent infections, hypogammaglobulinemia and severe diarrhea. Genome sequencing showed a heterozygous CTLA4 variant in exon 2. Abatacept therapy with prednisolone and cyclosporine was effective for diarrhea and autoimmune cytopenia. Conclusions A patient with CTLA4 variant might develop multiple central nervous system lesions including longitudinally‐extended spinal cord lesions. As there is effective targeted immunotherapy, a complete immunological work‐up is required for early diagnosis when a patient presents with central nervous system lesions and multi‐organ symptoms. An adult case of central nervous system lesions due to cytotoxic T‐lymphocyte antigen 4 haploinsufficiency was presented. This case suggests that patients with cytotoxic T‐lymphocyte antigen 4 haploinsufficiency might show steroid‐responsive long spinal lesions.