A20 haploinsufficiency (HA20)

Mutations in the TNFAIP3 gene have been found to cause haploinsufficiency of A20 (HA20). It’s an early-onset autoinflammatory disease resembling Behçet disease. The major phenotype of HA20 is Behçet disease–like symptoms, including a recurrent aphthous stomatitis (mouth ulcers), genital ulcers, and intestinal symptoms. Some patients present with not only the symptoms of autoinflammatory disorders but also several autoimmune-like symptoms. HA20 might be difficult to differentiate from other autoinflammatory disorders.

Patients with HA20 are juvenile-onset and partially resemble those with Behçet disease, but their phenotypes (phenotype is the observable characteristics of an organism that result from the interaction of its genotype [total genetic inheritance]) are distinct from those of classical Behçet disease. The patients with HA20 showed an excess production of proinflammatory cytokines. Proinflammatory cytokines are increased during flares.

Early-onset systemic inflammation, arthralgia/arthritis, recurrent oral, genital and/or gastrointestinal ulcers are the hallmark feature of HA20. Frequency and intensity of other clinical manifestations varied highly. Treatment regimens should be based on disease severity, and cytokine (small proteins including interleukins, lymphokines and cell signal molecules, which trigger inflammation) inhibitors are often required to control relapses.

The disorder results from inappropriate activation of inflammatory cytokines; treatment with tumor necrosis factor (TNF) inhibitors may be beneficial (summary by Zhou et al., 2016). 



1. Haploinsufficiency of A20 causes autoinflammatory and autoimmune disorders. Tomonori Kadowaki et al. The Journal of Allergy and Clinical  Immunology, April 2018 Volume 141, Issue 4, Pages 1485–1488.e11. https://www.jacionline.org/article/S0091-6749(17)31885-7/fulltext

2. Autoinflammatory Syndrome, Familial, Behcet-Like https://www.malacards.org/card/autoinflammatory_syndrome_familial_behcet_like

3. HA20: A Novel Autoinflammatory Disease Caused By Haploinsufficiency of A20, Encoded By TNFAIP3. Qing Zhou et al. ABSTRACT NUMBER: 899, Meeting: 2015 ACR/ARHP Annual Meeting


4. A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease. Ronald M. Laxer et al., Annals of the Rheumatic Diseases. https://ard.bmj.com/content/77/5/728