ESPE Abstracts

Background: A20 (HA20) haploinsufficiency is a disease that causes persistent inflammation throughout the body due to a deficiency of the A20 protein, which suppresses the production of inflammatory cytokines such as TNF-α. It was first reported in 2016 as an inherited autoinflammatory disease with Behcet's disease-like symptoms that develops at a young age and has been reported to be associated with autoimmune diseases such as Hashimoto's disease and systemic lupus erythematosus. The pathogenesis of this disease, which presents with a variety of clinical manifestations, is still unclear, and its treatment remains underdeveloped. We report a case involving an infant with HA20 whose diagnosis was triggered by the presentation of type 1 diabetes mellitus.

Case Report: An 11-month-old boy with diabetic ketoacidosis visited the emergency room of a regional hospital. Initial laboratory findings revealed venous blood gas pH of 7.2, BE of -21.0 mmol/L, HCO3^- of 4.3 mmol/L, blood glucose level of 547 mg/dL and HbA1c of 9.5%. The patient was transferred to our hospital and discharged after receiving sensor-augmented pump therapy with a confirmed diagnosis of type 1 diabetes. During outpatient follow-up, elevated liver enzymes were observed. Genetic testing revealed a heterozygous c.1831_1835 dup (p.Cys612TrpfsTer87) mutation in the TNFAIP3 gene, suggesting the possibility of autoimmune hepatitis caused by HA20. Subsequent examination revealed positive faecal occult blood and a folliculitis-like skin rash, and a diagnosis of HA20 was made. After a liver biopsy, treatment with prednisolone (PSL) and azathioprine was initiated, and although the patient’s liver enzymes tended to improve, his hyperglycaemia worsened, requiring an increase in the administration of insulin. Infliximab (IFX) was started, and the PSL was reduced after IFX was initiated. Currently, IFX has been changed to adalimumab because of the development of an infusion reaction when IFX was infused.

Conclusion: Type 1 diabetes mellitus patients with positivity for autoantibodies in infancy may have an underlying autoinflammatory disease. The identification of complications and genetic testing may be useful for confirming the diagnosis and initiating early treatment of the underlying disease. We believe that the use of biologics in the treatment of HA20 haploinsufficiency patients with type 1 diabetes mellitus may lead to better glycaemic control.