CASE REPORT article
Front. Pediatr.
Sec. Pediatric Immunology
Volume 13 - 2025 | doi: 10.3389/fped.2025.1624715
Exploring the Spectrum of A20 Haploinsufficiency in Children: A Case Series
Provisionally accepted
- Johns Hopkins Medicine, Johns Hopkins University, Baltimore, United States
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Haploinsufficiency of A20 (HA20), caused by TNFAIP3 mutations, is a rare autoinflammatory syndrome with highly variable, multisystem manifestations that often postpone recognition and definitive care. The A20 protein restrains NF-κB-mediated pro-inflammatory signaling therefore loss-of-function variants unleash widespread inflammation that can involve virtually any organ.Fewer than 200 cases have been reported worldwide, thus, clinicians have limited phenotypespecific guidance. We describe four unrelated patients evaluated at a single tertiary center, each carrying a distinct TNFAIP3 mutation and exhibiting a unique clinical picture ranging from mucocutaneous ulcerations and Behçet-like vasculitis to lupus-like autoimmunity and periodic fever with arthritis. Tailored therapies were selected to match the dominant inflammatory pathway and produced durable clinical remission in all cases. By linking genotype, phenotype, and therapeutic response, this case series broadens the clinical spectrum of HA20 and offers practical, phenotype-driven strategies to improve screening, diagnosis, and individualized management.
Keywords: A20 haploinsufficiency, Pediatrics, Genetic mutations, Clinical phenotypes, symptom-specific treatments
Received: 07 May 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Jayaraman and Balmuri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sahana Jayaraman, Johns Hopkins Medicine, Johns Hopkins University, Baltimore, United States
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