Clinical characteristics and genetic analysis of A20 haploinsufficiency

Pediatr Rheumatol Online J. 2021 May 24;19(1):75. doi: 10.1186/s12969-021-00558-6.

Abstract

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.

Keywords: A20 haploinsufficiency; Behçet-like syndrome; Tumor necrosis factor antagonists.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Arthritis / diagnosis
  • Arthritis / genetics
  • Arthritis / immunology
  • Autoantibodies* / analysis
  • Autoantibodies* / classification
  • Child
  • Child, Preschool
  • Exome Sequencing
  • Female
  • Gastrointestinal Diseases* / diagnosis
  • Gastrointestinal Diseases* / genetics
  • Gastrointestinal Diseases* / immunology
  • Genetic Predisposition to Disease
  • Haploinsufficiency / genetics*
  • Humans
  • Immunosuppressive Agents* / classification
  • Immunosuppressive Agents* / therapeutic use
  • Inflammatory Bowel Diseases* / diagnosis
  • Inflammatory Bowel Diseases* / genetics
  • Inflammatory Bowel Diseases* / immunology
  • Male
  • Monitoring, Immunologic / methods
  • Mutation
  • Spinal Diseases* / diagnosis
  • Spinal Diseases* / genetics
  • Spinal Diseases* / immunology
  • Treatment Outcome
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics*

Substances

  • Adrenal Cortex Hormones
  • Autoantibodies
  • Immunosuppressive Agents
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3