ArticleMolecular genetics and metabolism2017
Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots.
Article in Molecular genetics and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS.Annals of the rheumatic diseases · 2022Pooled it
- Clinical Characterization of a Multicenter International Cohort of Patients With Aicardi-Goutières Syndrome Homozygous for the RNASEH2B:p.Ala177Thr Variant: Early Clinical Markers of Disease Severity.Pediatric neurology · 2025Article
- Newborn Screening of X-Linked Adrenoleukodystrophy in Italy: Clinical and Biochemical Outcomes from a 4-Year Pilot Study.International journal of neonatal screening · 2025Article
- CNS disease associated with enhanced type I interferon signalling.The Lancet. Neurology · 2024Review
- Article
- IFN-signaling gene expression as a diagnostic biomarker for monogenic interferonopathies.JCI insight · 2024Article
- TREX1 is required for microglial cholesterol homeostasis and oligodendrocyte terminal differentiation in human neural assembloids.Molecular psychiatry · 2024Article
- Approaches to diagnosis for individuals with a suspected inherited white matter disorder.Handbook of clinical neurology · 2024Review
- Juvenile Dermatomyositis and Infantile Cerebral Palsy: Aicardi-Gouteres Syndrome, Type 5, with a Novel Mutation in SAMHD1-A Case Report.Biomedicines · 2023Article
- Clinical Non-penetrance Associated with Biallelic Mutations in the RNase H2 Complex.Journal of clinical immunology · 2023Article
- Age and gender-specific reference intervals for a panel of lysophosphatidylcholines estimated by tandem mass spectrometry in dried blood spots.Practical laboratory medicine · 2023Article
- SARS-CoV-2 mRNA-based vaccines in the Aicardi Goutières Syndrome.Molecular genetics and metabolism · 2022Article
- Hematologic abnormalities in Aicardi Goutières Syndrome.Molecular genetics and metabolism · 2022Article
- The type I interferonopathies: 10 years on.Nature reviews. Immunology · 2022Review
- Efficacy of baricitinib on chronic pericardial effusion in a patient with Aicardi-Goutières syndrome.Rheumatology (Oxford, England) · 2022Article
- Newborn Screening for X-Linked Adrenoleukodystrophy: Past, Present, and Future.International journal of neonatal screening · 2022Article
- ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy.The application of clinical genetics · 2022Review
- Very-Long-Chain Fatty Acids Quantification by Gas-Chromatography Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring.Frontiers in neurology · 2022Article
- Hepatic Involvement in Aicardi-Goutières Syndrome.Neuropediatrics · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 14 institutions in 7 countries.
Funding
Abstract
backgroundAicardi Goutières Syndrome (AGS) is a heritable interferonopathy associated with systemic autoinflammation causing interferon (IFN) elevation, central nervous system calcifications, leukodystrophy and severe neurologic sequelae. An infant with TREX1 mutations was recently found to have abnormal C26:0 lysophosphatidylcholine (C26:0 Lyso-PC) in a newborn screening platform for X-linked adrenoleukodystrophy, prompting analysis of this analyte in retrospectively collected samples from individuals affected by AGS.
methodsIn this study, we explored C26:0 Lyso-PC levels and IFN signatures in newborn blood spots and post-natal blood samples in 19 children with a molecular and clinical diagnosis of AGS and in the blood spots of 22 healthy newborns. We used Nanostring nCounter™ for IFN-induced gene analysis and a high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS) newborn screening platform for C26:0 Lyso-PC analysis.
resultsNewborn screening cards from patients across six AGS associated genes were collected, with a median disease presentation of 2months. Thirteen out of 19 (68%) children with AGS had elevations of first tier C26:0 Lyso-PC (>0.4μM), that would have resulted in a second screen being performed in a two tier screening system for X-linked adrenoleukodystrophy (X-ALD). The median (95%CI) of first tier C26:0 Lyso-PC values in AGS individuals (0.43μM [0.37-0.48]) was higher than that seen in controls (0.21μM [0.21-0.21]), but lower than X-ALD individuals (0.72μM [0.59-0.84])(p<0.001). Fourteen of 19 children had elevated expression of IFN signaling on blood cards relative to controls (Sensitivity 73.7%, 95%CI 51-88%, Specificity 95%, 95% CI 78-99%) including an individual with delayed disease presentation (36months of age). All five AGS patients with negative IFN signature at birth had RNASEH2B mutations. Consistency of agreement between IFN signature in neonatal and post-natal samples was high (0.85).
conclusionThis suggests that inflammatory markers in AGS can be identified in the newborn period, before symptom onset. Additionally, since C26:0 Lyso-PC screening is currently used in X-ALD newborn screening panels, clinicians should be alert to the fact that AGS infants may present as false positives during X-ALD screening.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.