However, it was soon realized that perforin deficiency entails other, more complex, functional consequences, leading to the development of type II familial hemophagocytic lymphohistiocytosis [16, 17, 20], which shares pathophysiological features with the macrophage activation syndrome, including interferon- (IFN-) γ overproduction. This evidence concerns the gene PRF1 and macrophage activation syndrome.