Majeed syndrome: first description in a patient of central-European ancestry

Objectives: We present the first case of a Majeed syndrome in a girl of central-European ancestry. Methods: Patient’s medical records were reviewed. A next-generation sequencing (NGS) panel for autoinflammatory diseases was performed and the mutation was confirmed by Sanger analysis. Freshly isolated monocytes were activated with lipopolysaccharide ± ATP. The concentration of inflammatory cytokines was assessed in monocyte supernatants. Results: A 2-year-old girl presented with pain in the lower limbs, increase of acute phase reactants and persistent microcytic anaemia. The MRI showed bilateral short time inversion recovery (STIR) hyper-intensity of the spongy osseous tissue of the femur, tibia, radius, ulna and astragalus. Bone marrow analysis revealed increased trilinear cellularity with signs of dyserythropoietic anaemia. The NGS panel detected the presence of two novel compound heterozygous mutations in the LPIN2 gene, confirmed by Sanger analysis. Treatment with anakinra was started with a prompt resolution of the clinical picture. Increased kinetics and concentration of IL-1β were observed in the patient’s monocytes compared with healthy controls, with a marked drop following the start of therapy. About 6 months after the start of the therapy, resolution of MRI findings, microcytic anaemia and dyserythropoiesis at bone marrow aspirate were observed. Conclusion: We describe the first case of Majeed syndrome in a patient of central-European ancestry. The functional test on circulating monocytes before and after therapy with anakinra confirmed pathogenicity of the mutation and the role of LPIN2 in the NLRP3 inflammasome activation. Anti-IL1 agents were effective, leading not only to the resolution of bone lesions but also to an improvement of dyserythropoiesis.