How does the purine metabolic checkpoint FAMIN prevent immunopathology?

Still's disease is a severe disease in children that starts with daily recurring high fever, a rash and lymph node enlargement, and morphs over weeks into a debilitating arthritis. Worse, virus infection can lead to an often fatal cytokine storm. Loss-of-function of FAMIN is the sole known cause for familial Still's disease. We discovered that FAMIN is an unprecedented enzyme involved in the metabolism of adenine and guanine, hence the nucleobases of the genetic code and energy currency of the cell. FAMIN is very ancient, with predecessors already present in bacteria. Its discovery changes our understanding of a very fundamental process of life. A partially active genetic variant of FAMIN is carried by ~6% of the population, and predisposes for Crohn's disease, an inflammatory bowel disease, and leprosy, a chronic infection. Here we explore how FAMIN defects predispose for these conditions, and how that might be prevented and treated.