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

Autor:	Drago E; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Italy, Genoa., Bertoni A; Center for autoinflammatory diseases and immunodeficiencies, IRCCS G. Gaslini Institute, Genova, Italy., Grossi A; Unità Operativa Semplice Dipartimentale (UOSD) Laboratory of Genetics and Genomics of Rare Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genova, Italy., Damasio MB; Department of Radiology, IRCCS Istituto Giannina Gaslini, Genova, Italy., Anfigeno L; Department of Radiology, IRCCS Istituto Giannina Gaslini, Genova, Italy., Miano M; Hematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Papa R; Center for autoinflammatory diseases and immunodeficiencies, IRCCS G. Gaslini Institute, Genova, Italy., Volpi S; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Italy, Genoa.; Center for autoinflammatory diseases and immunodeficiencies, IRCCS G. Gaslini Institute, Genova, Italy., Ceccherini I; Unità Operativa Semplice Dipartimentale (UOSD) Laboratory of Genetics and Genomics of Rare Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genova, Italy., Gattorno M; Center for autoinflammatory diseases and immunodeficiencies, IRCCS G. Gaslini Institute, Genova, Italy., Caorsi R; Center for autoinflammatory diseases and immunodeficiencies, IRCCS G. Gaslini Institute, Genova, Italy.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Sep 10. Date of Electronic Publication: 2024 Sep 10.
DOI:	10.1093/rheumatology/keae480
Abstrakt:	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 NGS panel for autoinflammatory diseases was performed and the mutation was confirmed by Sanger analysis. Freshly isolated monocytes were activated with LPS +/- ATP. The concentration of inflammatory cytokines was assessed in monocytes 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 STIR hyper-intensity of the spongy osseous tissue of femur, tibia, radius, ulna, and astragalus. Bone marrow analysis revealed increased trilinear cellularity with signs of dyserythropoietic anaemia. 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 was observed in the patient's monocytes compared with healthy controls, with a marked drop following the start of therapy. About six months after the start of the therapy, resolution of MRI findings, microcytic anaemia and dyserythropoiesis at bone marrow aspirate was 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 lesion but also to an improvement of dyserythropoiesis. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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