Abstract:

Objective To analyze the clinical characteristics and TNFAIP3 gene variation of 3 patients with A20 haploinsufficiency of A20 (HA20), so as to provide clues for clinical diagnosis and treatment. Methods The clinical manifestations, laboratory data and digestive endoscopy changes of 3 patients were collected. Whole exome sequencing (WES) was performed on the patients and their parents, and the pathogenic variants were verified by Sanger sequencing. Results All 3 patients were female, and the minimum age of onset was 13 days after birth. No ocular lesions were found in any of the patients who presented with fever, diarrhea, and mucosa-stained feces. Digestive endoscopy in patient 1 showed frost-like ulcers of the duodenum bulb, hemorrhagic gastritis, multiple ulcers in the jejunum and lower ileum, and colonoscopy revealed red hyperaemia in the ileocecum. Digestive endoscopy of patient 2 showed no abnormalities in the stomach and small intestine, and multiple ulcers were found in multiple ulcers in colon. Patient 3 did not undergo digestive endoscopy. WES showed that all patients carried heterozygous variants of TNFAIP3 gene: c.811C>T, p.R271X (spontaneous variant), c.292_295dup, p.G99EfsX3 (a variant inherited from mother) and c.133C>T, p.R45X (a variant inherited from mother). According to ACMG (American College of Medical Genetics and Genomics) guidelines, they are classified as pathogenic variation, suspected pathogenic variation, and pathogenic variation, respectively. Patient 1 was treated with methylprednisolone which was ineffective, and was then treated with infliximab; patient 2 was given adalimumab after methylprednisolone-induced remission, and patient 3 was switched to thalidomide after methylprednisolone-induced remission. The clinical symptoms of 3 patients were relieved, and their growth and development were improved. Conclusion Children with recurrent fever, oral ulcers and refractory diarrhea should be alert to HA20, and genetic testing of suspected patients is helpful for early diagnosis.

Key words: fever, refractory diarrhea, recurrent oral ulcer, whole exome sequencing, TNFAIP3 gene