In conclusion, mutations in NBAS are delineated as a previously unknown cause of acute liver failure with onset in childhood triggered by febrile infections. It is possible that the affected individuals reported in this study present the severe end of the phenotypic spectrum. Notably, in families F8 and F9, two older siblings had died from acute liver failure, aged 14 and 11 months. Unfortunately, no material was available for diagnostics from the deceased individuals. However, the finding of NBAS mutations in their siblings suggests NBAS-induced ALF. Hence, these individuals might provide examples for a lethal course of NBAS deficiency. We recommended sequencing NBAS in cases of ALF in infancy and childhood of unknown cause, especially in individuals with fever-associated ALF and/or RALF.