Our molecular, cellular, immunological, and clinical studies of two unrelated patients with inherited IRF1 deficiency do not exclude the possibility of predisposition to unusual and/or severe clinical diseases caused by viruses that have not been tested in vitro, or that have not been encountered by the patients in vivo, or both, or even such diseases caused by seemingly benign viruses in different infection conditions (e.g. high levels of inoculum, atypical route of infection, infection before vaccination), in these or other IRF1-deficient patients. The gene discussed is IRF1; the disease is hyperinsulinemic hypoglycemia, familial, 4.