While active viral infection is usually excluded before a diagnosis of AGS or RNaseT2-deficient leukodystrophy can be made, it is possible that exposure to commonplace, low-virulence viruses could serve as a risk factor—or even a trigger—for activation of type I interferon response in patients that are already genetically predisposed to interferonopathies. Here, RNASET2 is linked to leukodystrophy.