Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots.

•Aicardi Goutières Syndrome (AGS) is a heritable interferonopathy associated with systemic autoinflammation.•AGS results in interferon (IFN) elevation, CNS calcifications, leukodystrophy and severe neurologic sequelae.•An infant with TREX1 mutations was found to have abnormal C26:0 Lyso-PC on newborn screening.•This prompted analysis of this analyte in retrospectively collected samples from individuals affected by AGS.•Thirteen out of 19 (68%) children with AGS had elevations of first tier C26:0 Lyso-PC (>0.4µM).•This suggests that inflammatory markers in AGS can be identified in the newborn period, before symptom onset.•Additionally, clinicians should be alert that AGS infants may present as false positives during X-ALD screening.