Hematologic abnormalities in Aicardi Goutières Syndrome
Laura A Adang1, Francesco Gavazzi1, Russell D'Aiello1
1Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Molecular Genetics and Metabolism
|July 5, 2022
Summary
Aicardi Goutières Syndrome (AGS) commonly causes multilineage cytopenias, including neutropenia and anemia, throughout a patient's life. Careful monitoring of blood counts is essential, especially during treatment with janus kinase inhibitors like baricitinib.
Area of Science:
- Genetics
- Immunology
- Hematology
Background:
- Aicardi Goutières Syndrome (AGS) is a common genetic interferonopathy causing systemic inflammation and neurologic disability.
- Understanding AGS is challenging due to its broad clinical spectrum and the emergence of genotype-specific complications.
- Multilineage cytopenias are a serious, yet poorly understood, complication of AGS.
Purpose of the Study:
- To characterize hematologic abnormalities in Aicardi Goutières Syndrome (AGS) across different genotypes.
- To differentiate disease-related cytopenias from treatment-related effects, particularly with janus kinase inhibitor (baricitinib) use.
- To identify patterns of hematologic abnormalities throughout the lifespan of individuals with AGS.
Main Methods:
- Collected longitudinal hematologic laboratory data from 142 individuals with molecularly-confirmed AGS.
- Included pre- and post-treatment data for a subset (n=52) treated with baricitinib as part of a clinical trial.
- Compared laboratory values across genotypes and baricitinib exposure, grading abnormalities using CTCAE v5.0.
Main Results:
- Anemia, thrombocytopenia, and neutropenia were common AGS-related cytopenias, occurring beyond the neonatal period.
- Neutropenia was most frequent in the SAMHD1 genotype and increased with baricitinib exposure.
- While moderate-to-severe neutropenia, anemia, and leukopenia were more frequent on baricitinib, they were rarely clinically significant.
Conclusions:
- AGS is associated with lifelong multilineage cytopenias, necessitating comprehensive hematologic monitoring.
- Hematologic abnormalities on baricitinib were generally mild and rarely consequential, but require careful observation.
- AGS should be considered in pediatric cases of unexplained neurologic impairment with co-occurring hematologic abnormalities.
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