Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies.

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C＞T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.

Evaluation of high resolution esophageal manometry in peroral endoscopic myotomy for pediatric achalasia of cardia / 中华消化内镜杂志

Objective:To evaluate high resolution esophageal manometry (HREM) in peroral endoscopic myotomy (POEM) for pediatric achalasia of cardia (AC).Methods:Data of 30 AC children who received POEM in Xi′an Children′s Hospital from January 2013 to September 2019 were reviewed. HREM was performed before and 6 months after POEM. Preoperative and postoperative lower esophageal sphincter pressure (LESP), 4-second integrated relaxation pressure (4sIRP), Eckardt scores and nutritional status were compared.Results:Children with AC aged between 4-14 years. Postoperative LESP was 5.50±1.13 mmHg (1 mmHg=0.133 kPa), which was significantly lower than that before operation (26.23±4.47 mmHg) with significant difference ( t=-24.623, P<0.001). Postoperative median 4sIRP was 5 mmHg, which was 20 mmHg lower than that before operation (25 mmHg) with significant difference ( Z=-4.786, P<0.001). Postoperative median Eckardt symptom score decreased significantly compared with that before (1 VS 8, Z=-4.796, P<0.001). Severe malnutrition of the AC children improved evidently to normal( Z=-5.166, P<0.001). Conclusion:POEM can significantly improve the characteristics of esophageal dynamics in children with AC, and HREM can be an important indicator for follow-up evaluation of POEM.