Abstract
PurposeTo evaluate the clinical and genetic characteristics of 3 children with Haploinsufficiency of A20 (HA20). Methods:The clinical and genetic testing data of 3 children with HA20 treated at Capital Institute of Pediatrics (CIP) between August 2016 and October 2019 were retrospectively analysed.ResultPatient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. Regarding laboratory tests, patients were found to have elevated white blood cell (WBC) count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The CRP and ESR was reported to be high in all the patients. The WBC was reported to be high in patient 1 and 3. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that all three patients had heterozygous mutation in TNFAIP3 gene. As for the treatment, patient 1 was treated with TNFα antagonist, patient 2 was treated with TNF α antagonist and sulfasalazine, and patient 3 was treated with corticosteroids and thalidomide. Patients 1 and 2 were followed for four and 3 months, respectively. There was an improvement in joint and gastrointestinal symptoms; inflammatory indices and rheumatoid factor (RF) were normal, and dsDNA and Coombs test became negative. Patient 3 was treated at another hospital and showed gradual improvement in oral ulcers and perianal abscesses.ConclusionHA20 is a single-gene auto-inflammatory disease caused by mutation in tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) gene. It may present as Behçet-like syndrome and resemble various other autoimmune diseases as well. Corticosteroids and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with early-age onset or Behçet-like syndrome to achieve early diagnosis and accurate treatment.
Highlights
A20 haploinsufficiency is an autosomal dominant hereditary disease caused by a pathological mutation in tumour necrosis factor (TNF)-α-induced protein 3 gene [1, 2]
A20 haploinsufficiency (HA20) is an autosomal dominant genetic disease caused by mutation of TNF-αinduced protein 3 (TNFAIP3) gene [5,6,7]
When stimulated by various inflammatory factors, nuclear factor (NF)-κB can induce the expression of various genes, resulting in the production of cytokines that participate in inflammatory response
Summary
A20 haploinsufficiency is an autosomal dominant hereditary disease caused by a pathological mutation in tumour necrosis factor (TNF)-α-induced protein 3 gene [1, 2]. Production of nuclear factor (NF)-κB regulatory protein A20 encoded by TNFAIP3 gene is insufficient, and clinical signs resemble Behçet’s disease [3, 4]. These clinical signs appear earlier in HA20, and the age of disease onset is most likely before 10, including recurrent appearance of painful oral, genital, and/or gastrointestinal ulcers. Two of three patients were treated with biologics, and showed significant clinical improvement and few side effects. The clinical and genetic testing results of all three patients were analysed in order to improve our understanding of diagnosis and treatment of HA20
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