In sepsis-negative neonates with early multisystem inflammation, the differential should therefore include monogenic autoinflammatory syndromes (NLRP3/NOMID (Goldbach-Mansky et al., 2006; Wm et al., 2007), NLRC4 gain-of-function (Canna et al., 2014; Romberg et al., 2014)), primary immunodeficiencies (e.g., SH2D1A/XIAP, RAG1/IL27RA), inborn errors of metabolism, and congenital leukemia (Brown et al., 2019; Brown, 2021), alongside familial HLH. The gene discussed is NLRP3; the disease is Sepsis.