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Published on: August 15, 2019
Clinical characteristics and genetic analysis of A20 haploinsufficiency
Dan Zhang1, Gaixiu Su2, Zhixuan Zhou1
1Capital Institute of Pediatrics, 2 yabao road, Chaoyang District, Beijing, China.
Insights
Haploinsufficiency of A20 (HA20) is an autoinflammatory disease caused by TNFAIP3 gene mutations. Early genetic testing is crucial for diagnosing and treating children with Behçet-like symptoms.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Haploinsufficiency of A20 (HA20) is a rare autoinflammatory disorder.
- It stems from mutations in the TNFAIP3 gene, which regulates inflammatory responses.
Observation:
- Three pediatric patients presented with diverse symptoms including arthritis, inflammatory bowel disease, lupus-like syndrome, and recurrent ulcers.
- Elevated inflammatory markers (CRP, ESR, WBC) and autoantibodies were noted in some patients.
- Genetic analysis confirmed heterozygous TNFAIP3 mutations in all three cases.
Findings:
- The study highlights the clinical heterogeneity of HA20, mimicking Behçet's disease and other autoimmune conditions.
- Treatment with TNFα antagonists, corticosteroids, and immunosuppressants showed positive clinical responses.
- Inflammatory markers and autoantibodies normalized in responding patients.
Implications:
- Early whole-exome genetic testing is recommended for children with early-onset or Behçet-like autoinflammatory syndromes.
- Accurate genetic diagnosis facilitates timely and targeted therapeutic interventions.
- Understanding TNFAIP3 mutations improves management of autoinflammatory diseases.
Purpose:
To 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.
Result:
Patient 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.
Conclusion:
HA20 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.
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