OP0098 Clinical picture and spectrum of conditions associated with nlrp12 gene mutations

Background NLRP12-related autoinflammatory disease (NLRP12-AID) is an exceptionally rare autosomal-dominant disorder caused by germ-line mutations in NLRP12 gene. Very few patients with NLRP12-AD have been identified worldwide, therefore there is a scarcity of data on phenotypic presentation of this syndrome. Objectives Here we provide evidence that NLRP12-AID may have clinical manifestations characteristic for primary immune deficiencies (PID). Methods 246 children with periodic fever (PF) of unknown origin were subjects to the next generation sequencing (NGS) analysis; 213 of these patients had signs of primary immunodeficiency (PID) manifested by recurrent infections, while 33 kids had isolated PF. The NGS panel was composed of 302 genes implicated in PID and/or AID. Results NLRP12 variants were detected in 20 cases (see the table 1). Median age of first AID-related fever episode was 12 months, ranging from 2 months to 13 years. Increased association with immune-mediated diseases (n=15, 75%) was observed. Nine patients demonstrated increased susceptibility to infection and two children suffered from Crohn’s disease. Administration of short courses of NSAID or corticosteroids resulted in resolution of the disease flare. In one severe case canakinumab (anti-interleukine-1β antibody) was successfully used. Conclusions Significant number of patients with genetically assigned diagnosis of NLPR12-AID have clinical features which close resemble PID. This phenotypic overlap may result in underdiagnosis of NLPR12-AID among patients with PID. Acknowledgements This work has been supported by Russian Foundation for Basic Research (grant number RFBR 16–04–00 159a). Disclosure of Interest None declared